Author: "Tanic, M" / Publication Year Range: Last 3 years - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Tanic, M"' showing total 17 results

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17 results on '"Tanic, M"'

1. Mixed responses to targeted therapy driven by chromosomal instability through p53 dysfunction and genome doubling

Author: Hobor, S, Al Bakir, M, Hiley, C, Skrzypski, M, Frankell, A, Bakker, B, Watkins, T, Markovets, A, Dry, J, Brown, A, van der Aart, J, van den Bos, H, Spierings, D, Oukrif, D, Novelli, M, Chakrabarti, T, Rabinowitz, A, Ait Hassou, L, Litiere, S, Kerr, D, Tan, L, Kelly, G, Moore, D, Renshaw, M, Venkatesan, S, Hill, W, Huebner, A, Martinez-Ruiz, C, Black, J, Wu, W, Angelova, M, Mcgranahan, N, Downward, J, Chmielecki, J, Barrett, C, Litchfield, K, Chew, S, Blakely, C, de Bruin, E, Foijer, F, Vousden, K, Bivona, T, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Tufail, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Shaw, J, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, French, J, Gilbert, K, Naidu, B, Patel, A, Osman, A, Enstone, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totton, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Paiva-Correia, A, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Brown, K, Carter, M, Chaturvedi, A, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Dive, C, Aerts, H, Schwarz, R, Kaufmann, T, Wilson, G, Rosenthal, R, Van Loo, P, Birkbak, N, Szallasi, Z, Kisistok, J, Sokac, M, Salgado, R, Diossy, M, Demeulemeester, J, Bunkum, A, Dwornik, A, Magness, A, Rowan, A, Karamani, A, Toncheva, A, Chain, B, Castignani, C, Bailey, C, Abbosh, C, Puttick, C, Weeden, C, Lee, C, Richard, C, Naceur-Lombardelli, C, Pearce, D, Karagianni, D, Biswas, D, Levi, D, Larose Cadieux, E, Lim, E, Colliver, E, Nye, E, Galvez-Cancino, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Lowe, H, Matos, I, Noorani, I, Goldman, J, Reading, J, Rane, J, Nicod, J, Hartley, J, Peggs, K, Enfield, K, Selvaraju, K, Thol, K, Ng, K, Chen, K, Dijkstra, K, Grigoriadis, K, Thakkar, K, Ensell, L, Shah, M, Litovchenko, M, Jamal-Hanjani, M, Werner Sunderland, M, Huska, M, Hill, M, Dietzen, M, Leung, M, Escudero, M, Tanic, M, Sivakumar, M, Chervova, O, Lucas, O, Pich, O, Al-Sawaf, O, Prymas, P, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Vendramin, R, Saghafinia, S, Gamble, S, Veeriah, S, Ung, S, Quezada, S, Vanloo, S, Hessey, S, Ward, S, Harries, S, Boeing, S, Beck, S, Bola, S, Karasaki, T, Denner, T, Marafioti, T, Jones, T, Spanswick, V, Barbe, V, Lu, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Martinoni Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Kaplar, Z, Bandula, S, Hackshaw, A, Hacker, A, Sharp, A, Smith, S, Kaur Dhanda, H, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Richards, J, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Nicholson, A, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Kidd, A, Dick, C, Le Quesne, J, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Hynds, R, Kanu, N, Zaccaria, S, Gronroos, E, Swanton, C, Hobor S., Al Bakir M., Hiley C. T., Skrzypski M., Frankell A. M., Bakker B., Watkins T. B. K., Markovets A., Dry J. R., Brown A. P., van der Aart J., van den Bos H., Spierings D., Oukrif D., Novelli M., Chakrabarti T., Rabinowitz A. H., Ait Hassou L., Litiere S., Kerr D. L., Tan L., Kelly G., Moore D. A., Renshaw M. J., Venkatesan S., Hill W., Huebner A., Martinez-Ruiz C., Black J. R. M., Wu W., Angelova M., McGranahan N., Downward J., Chmielecki J., Barrett C., Litchfield K., Chew S. K., Blakely C. M., de Bruin E. C., Foijer F., Vousden K. H., Bivona T. G., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Tufail M., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Shaw J. A., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., French J., Gilbert K., Naidu B., Patel A. J., Osman A., Enstone C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totton N., Montero A., Smith E., Fontaine E., Granato F., Paiva-Correia A., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P. A. J., Brown K. D., Carter M., Chaturvedi A., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Dive C., Aerts H. J. W. L., Schwarz R. F., Kaufmann T. L., Wilson G. A., Rosenthal R., Van Loo P., Birkbak N. J., Szallasi Z., Kisistok J., Sokac M., Salgado R., Diossy M., Demeulemeester J., Bunkum A., Dwornik A., Magness A., Rowan A. J., Karamani A., Toncheva A., Chain B., Castignani C., Bailey C., Abbosh C., Puttick C., Weeden C. E., Lee C., Richard C., Naceur-Lombardelli C., Pearce D. R., Karagianni D., Biswas D., Levi D., Larose Cadieux E., Lim E. L., Colliver E., Nye E., Galvez-Cancino F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G. -T., Lowe H. L., Matos I. G., Noorani I., Goldman J., Reading J. L., Rane J. K., Nicod J., Hartley J. A., Peggs K. S., Enfield K. S. S., Selvaraju K., Thol K., Ng K. W., Chen K., Dijkstra K., Grigoriadis K., Thakkar K., Ensell L., Shah M., Litovchenko M., Jamal-Hanjani M., Werner Sunderland M., Huska M. R., Hill M. S., Dietzen M., Leung M. M., Escudero M., Tanic M., Sivakumar M., Chervova O., Lucas O., Pich O., Al-Sawaf O., Prymas P., Hobson P., Pawlik P., Stone R. K., Bentham R., Vendramin R., Saghafinia S., Gamble S., Veeriah S., Ung S. K. A., Quezada S. A., Vanloo S., Hessey S., Ward S., Harries S., Boeing S., Beck S., Bola S. K., Karasaki T., Denner T., Marafioti T., Jones T. P., Spanswick V., Barbe V., Lu W. -T., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Martinoni Hoogenboom E., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Gorman P., Khiroya R., Stephens R. C. M., Wong Y. N. S., Kaplar Z., Bandula S., Hackshaw A., Hacker A. -M., Sharp A., Smith S., Kaur Dhanda H., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Richards J., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Nicholson A. G., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Kidd A., Dick C., Le Quesne J., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Hynds R. E., Kanu N., Zaccaria S., Gronroos E., Swanton C., Hobor, S, Al Bakir, M, Hiley, C, Skrzypski, M, Frankell, A, Bakker, B, Watkins, T, Markovets, A, Dry, J, Brown, A, van der Aart, J, van den Bos, H, Spierings, D, Oukrif, D, Novelli, M, Chakrabarti, T, Rabinowitz, A, Ait Hassou, L, Litiere, S, Kerr, D, Tan, L, Kelly, G, Moore, D, Renshaw, M, Venkatesan, S, Hill, W, Huebner, A, Martinez-Ruiz, C, Black, J, Wu, W, Angelova, M, Mcgranahan, N, Downward, J, Chmielecki, J, Barrett, C, Litchfield, K, Chew, S, Blakely, C, de Bruin, E, Foijer, F, Vousden, K, Bivona, T, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Tufail, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Shaw, J, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, French, J, Gilbert, K, Naidu, B, Patel, A, Osman, A, Enstone, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totton, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Paiva-Correia, A, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Brown, K, Carter, M, Chaturvedi, A, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Dive, C, Aerts, H, Schwarz, R, Kaufmann, T, Wilson, G, Rosenthal, R, Van Loo, P, Birkbak, N, Szallasi, Z, Kisistok, J, Sokac, M, Salgado, R, Diossy, M, Demeulemeester, J, Bunkum, A, Dwornik, A, Magness, A, Rowan, A, Karamani, A, Toncheva, A, Chain, B, Castignani, C, Bailey, C, Abbosh, C, Puttick, C, Weeden, C, Lee, C, Richard, C, Naceur-Lombardelli, C, Pearce, D, Karagianni, D, Biswas, D, Levi, D, Larose Cadieux, E, Lim, E, Colliver, E, Nye, E, Galvez-Cancino, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Lowe, H, Matos, I, Noorani, I, Goldman, J, Reading, J, Rane, J, Nicod, J, Hartley, J, Peggs, K, Enfield, K, Selvaraju, K, Thol, K, Ng, K, Chen, K, Dijkstra, K, Grigoriadis, K, Thakkar, K, Ensell, L, Shah, M, Litovchenko, M, Jamal-Hanjani, M, Werner Sunderland, M, Huska, M, Hill, M, Dietzen, M, Leung, M, Escudero, M, Tanic, M, Sivakumar, M, Chervova, O, Lucas, O, Pich, O, Al-Sawaf, O, Prymas, P, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Vendramin, R, Saghafinia, S, Gamble, S, Veeriah, S, Ung, S, Quezada, S, Vanloo, S, Hessey, S, Ward, S, Harries, S, Boeing, S, Beck, S, Bola, S, Karasaki, T, Denner, T, Marafioti, T, Jones, T, Spanswick, V, Barbe, V, Lu, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Martinoni Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Kaplar, Z, Bandula, S, Hackshaw, A, Hacker, A, Sharp, A, Smith, S, Kaur Dhanda, H, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Richards, J, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Nicholson, A, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Kidd, A, Dick, C, Le Quesne, J, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Hynds, R, Kanu, N, Zaccaria, S, Gronroos, E, Swanton, C, Hobor S., Al Bakir M., Hiley C. T., Skrzypski M., Frankell A. M., Bakker B., Watkins T. B. K., Markovets A., Dry J. R., Brown A. P., van der Aart J., van den Bos H., Spierings D., Oukrif D., Novelli M., Chakrabarti T., Rabinowitz A. H., Ait Hassou L., Litiere S., Kerr D. L., Tan L., Kelly G., Moore D. A., Renshaw M. J., Venkatesan S., Hill W., Huebner A., Martinez-Ruiz C., Black J. R. M., Wu W., Angelova M., McGranahan N., Downward J., Chmielecki J., Barrett C., Litchfield K., Chew S. K., Blakely C. M., de Bruin E. C., Foijer F., Vousden K. H., Bivona T. G., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Tufail M., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Shaw J. A., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., French J., Gilbert K., Naidu B., Patel A. J., Osman A., Enstone C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totton N., Montero A., Smith E., Fontaine E., Granato F., Paiva-Correia A., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P. A. J., Brown K. D., Carter M., Chaturvedi A., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Dive C., Aerts H. J. W. L., Schwarz R. F., Kaufmann T. L., Wilson G. A., Rosenthal R., Van Loo P., Birkbak N. J., Szallasi Z., Kisistok J., Sokac M., Salgado R., Diossy M., Demeulemeester J., Bunkum A., Dwornik A., Magness A., Rowan A. J., Karamani A., Toncheva A., Chain B., Castignani C., Bailey C., Abbosh C., Puttick C., Weeden C. E., Lee C., Richard C., Naceur-Lombardelli C., Pearce D. R., Karagianni D., Biswas D., Levi D., Larose Cadieux E., Lim E. L., Colliver E., Nye E., Galvez-Cancino F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G. -T., Lowe H. L., Matos I. G., Noorani I., Goldman J., Reading J. L., Rane J. K., Nicod J., Hartley J. A., Peggs K. S., Enfield K. S. S., Selvaraju K., Thol K., Ng K. W., Chen K., Dijkstra K., Grigoriadis K., Thakkar K., Ensell L., Shah M., Litovchenko M., Jamal-Hanjani M., Werner Sunderland M., Huska M. R., Hill M. S., Dietzen M., Leung M. M., Escudero M., Tanic M., Sivakumar M., Chervova O., Lucas O., Pich O., Al-Sawaf O., Prymas P., Hobson P., Pawlik P., Stone R. K., Bentham R., Vendramin R., Saghafinia S., Gamble S., Veeriah S., Ung S. K. A., Quezada S. A., Vanloo S., Hessey S., Ward S., Harries S., Boeing S., Beck S., Bola S. K., Karasaki T., Denner T., Marafioti T., Jones T. P., Spanswick V., Barbe V., Lu W. -T., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Martinoni Hoogenboom E., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Gorman P., Khiroya R., Stephens R. C. M., Wong Y. N. S., Kaplar Z., Bandula S., Hackshaw A., Hacker A. -M., Sharp A., Smith S., Kaur Dhanda H., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Richards J., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Nicholson A. G., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Kidd A., Dick C., Le Quesne J., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Hynds R. E., Kanu N., Zaccaria S., Gronroos E., and Swanton C.
Abstract: The phenomenon of mixed/heterogenous treatment responses to cancer therapies within an individual patient presents a challenging clinical scenario. Furthermore, the molecular basis of mixed intra-patient tumor responses remains unclear. Here, we show that patients with metastatic lung adenocarcinoma harbouring co-mutations of EGFR and TP53, are more likely to have mixed intra-patient tumor responses to EGFR tyrosine kinase inhibition (TKI), compared to those with an EGFR mutation alone. The combined presence of whole genome doubling (WGD) and TP53 co-mutations leads to increased genome instability and genomic copy number aberrations in genes implicated in EGFR TKI resistance. Using mouse models and an in vitro isogenic p53-mutant model system, we provide evidence that WGD provides diverse routes to drug resistance by increasing the probability of acquiring copy-number gains or losses relative to non-WGD cells. These data provide a molecular basis for mixed tumor responses to targeted therapy, within an individual patient, with implications for therapeutic strategies.
Published: 2024

2. The artificial intelligence-based model ANORAK improves histopathological grading of lung adenocarcinoma

Author: Pan, X, Abduljabbar, K, Coelho-Lima, J, Grapa, A, Zhang, H, Cheung, A, Baena, J, Karasaki, T, Wilson, C, Sereno, M, Veeriah, S, Aitken, S, Hackshaw, A, Nicholson, A, Jamal-Hanjani, M, Le Quesne, J, Janes, S, Hacker, A, Sharp, A, Smith, S, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Lim, E, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Kidd, A, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Dick, C, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Tufail, M, Scotland, M, Boyles, R, Rathinam, S, Fennell, D, Marrone, D, Dulloo, S, Matharu, G, Shaw, J, Riley, J, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Papadatos-Pastos, D, Wilson, J, Ahmad, T, French, J, Gilbert, K, Naidu, B, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Paiva-Correia, A, Chaturvedi, A, Priest, L, Oliveira, P, Gomes, F, Brown, K, Carter, M, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Dive, C, Aerts, H, Schwarz, R, Kaufmann, T, Van Loo, P, Wilson, G, Rosenthal, R, Rowan, A, Bailey, C, Lee, C, Colliver, E, Enfield, K, Hill, M, Angelova, M, Pich, O, Leung, M, Frankell, A, Hiley, C, Zhai, H, Bakir, M, Birkbak, N, Lucas, O, Huebner, A, Puttick, C, Grigoriadis, K, Dietzen, M, Biswas, D, Athanasopoulou, F, Ward, S, Demeulemeester, J, Castignani, C, Cadieux, E, Kisistok, J, Sokac, M, Szallasi, Z, Diossy, M, Salgado, R, Stewart, A, Magness, A, Weeden, C, Levi, D, Gronroos, E, Noorani, I, Goldman, J, Escudero, M, Hobson, P, Vendramin, R, Boeing, S, Denner, T, Barbe, V, Lu, W, Hill, W, Naito, Y, Ramsden, Z, Kassiotis, G, Dwornik, A, Karamani, A, Chain, B, Pearce, D, Karagianni, D, Galvez-Cancino, F, Stavrou, G, Mastrokalos, G, Lowe, H, Matos, I, Reading, J, Hartley, J, Selvaraju, K, Chen, K, Ensell, L, Shah, M, Litovchenko, M, Chervova, O, Pawlik, P, Hynds, R, Gamble, S, Ung, S, Bola, S, Spanswick, V, Wu, Y, Al-Sawaf, O, Jones, T, Beck, S, Tanic, M, Marafioti, T, Borg, E, Falzon, M, Khiroya, R, Toncheva, A, Abbosh, C, Richard, C, Naceur-Lombardelli, C, Gimeno-Valiente, F, Thakkar, K, Sunderland, M, Sivakumar, M, Kanu, N, Prymas, P, Saghafinia, S, Vanloo, S, Lam, J, Liu, W, Bunkum, A, Hessey, S, Zaccaria, S, Martinez-Ruiz, C, Black, J, Thol, K, Bentham, R, Litchfield, K, Mcgranahan, N, Quezada, S, Forster, M, Lee, S, Herrero, J, Nye, E, Stone, R, Nicod, J, Rane, J, Peggs, K, Ng, K, Dijkstra, K, Huska, M, Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Gorman, P, Stephens, R, Wong, Y, Kaplar, Z, Bandula, S, Watkins, T, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Swanton, C, Yuan, Y, Moore, D, Pan X., AbdulJabbar K., Coelho-Lima J., Grapa A. -I., Zhang H., Cheung A. H. K., Baena J., Karasaki T., Wilson C. R., Sereno M., Veeriah S., Aitken S. J., Hackshaw A., Nicholson A. G., Jamal-Hanjani M., Le Quesne J., Janes S. M., Hacker A. -M., Sharp A., Smith S., Dhanda H. K., Chan K., Pilotti C., Leslie R., Chuter D., MacKenzie M., Chee S., Alzetani A., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Kidd A., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Dick C., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Tufail M., Scotland M., Boyles R., Rathinam S., Fennell D. A., Wilson C., Marrone D., Dulloo S., Matharu G., Shaw J. A., Riley J., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Papadatos-Pastos D., Wilson J., Ahmad T., French J., Gilbert K., Naidu B., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Paiva-Correia A., Chaturvedi A., Priest L., Oliveira P., Gomes F., Brown K., Carter M., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Dive C., Aerts H. J. W. L., Schwarz R. F., Kaufmann T. L., Van Loo P., Wilson G. A., Rosenthal R., Rowan A., Bailey C., Lee C., Colliver E., Enfield K. S. S., Hill M. S., Angelova M., Pich O., Leung M., Frankell A. M., Hiley C. T., Lim E. L., Zhai H., Bakir M. A., Birkbak N. J., Lucas O., Huebner A., Puttick C., Grigoriadis K., Dietzen M., Biswas D., Athanasopoulou F., Ward S., Demeulemeester J., Castignani C., Cadieux E. L., Kisistok J., Sokac M., Szallasi Z., Diossy M., Salgado R., Stewart A., Magness A., Weeden C. E., Levi D., Gronroos E., Noorani I., Goldman J., Escudero M., Hobson P., Vendramin R., Boeing S., Denner T., Barbe V., Lu W. -T., Hill W., Naito Y., Ramsden Z., Kassiotis G., Dwornik A., Karamani A., Chain B., Pearce D. R., Karagianni D., Galvez-Cancino F., Stavrou G., Mastrokalos G., Lowe H. L., Matos I. G., Reading J. L., Hartley J. A., Selvaraju K., Chen K., Ensell L., Shah M., Litovchenko M., Chervova O., Pawlik P., Hynds R. E., Gamble S., Ung S. K. A., Bola S. K., Spanswick V., Wu Y., Al-Sawaf O., Jones T. P., Beck S., Tanic M., Marafioti T., Borg E., Falzon M., Khiroya R., Toncheva A., Abbosh C., Richard C., Naceur-Lombardelli C., Gimeno-Valiente F., Thakkar K., Sunderland M. W., Sivakumar M., Kanu N., Prymas P., Saghafinia S., Vanloo S., Lam J. M., Liu W. K., Bunkum A., Hessey S., Zaccaria S., Martinez-Ruiz C., Black J. R. M., Thol K., Bentham R., Litchfield K., McGranahan N., Quezada S. A., Forster M. D., Lee S. M., Herrero J., Nye E., Stone R. K., Nicod J., Rane J. K., Peggs K. S., Ng K. W., Dijkstra K., Huska M. R., Hoogenboom E. M., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Gorman P., Stephens R. C. M., Wong Y. N. S., Kaplar Z., Bandula S., Watkins T. B. K., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Swanton C., Yuan Y., Moore D. A., Pan, X, Abduljabbar, K, Coelho-Lima, J, Grapa, A, Zhang, H, Cheung, A, Baena, J, Karasaki, T, Wilson, C, Sereno, M, Veeriah, S, Aitken, S, Hackshaw, A, Nicholson, A, Jamal-Hanjani, M, Le Quesne, J, Janes, S, Hacker, A, Sharp, A, Smith, S, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Lim, E, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Kidd, A, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Dick, C, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Tufail, M, Scotland, M, Boyles, R, Rathinam, S, Fennell, D, Marrone, D, Dulloo, S, Matharu, G, Shaw, J, Riley, J, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Papadatos-Pastos, D, Wilson, J, Ahmad, T, French, J, Gilbert, K, Naidu, B, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Paiva-Correia, A, Chaturvedi, A, Priest, L, Oliveira, P, Gomes, F, Brown, K, Carter, M, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Dive, C, Aerts, H, Schwarz, R, Kaufmann, T, Van Loo, P, Wilson, G, Rosenthal, R, Rowan, A, Bailey, C, Lee, C, Colliver, E, Enfield, K, Hill, M, Angelova, M, Pich, O, Leung, M, Frankell, A, Hiley, C, Zhai, H, Bakir, M, Birkbak, N, Lucas, O, Huebner, A, Puttick, C, Grigoriadis, K, Dietzen, M, Biswas, D, Athanasopoulou, F, Ward, S, Demeulemeester, J, Castignani, C, Cadieux, E, Kisistok, J, Sokac, M, Szallasi, Z, Diossy, M, Salgado, R, Stewart, A, Magness, A, Weeden, C, Levi, D, Gronroos, E, Noorani, I, Goldman, J, Escudero, M, Hobson, P, Vendramin, R, Boeing, S, Denner, T, Barbe, V, Lu, W, Hill, W, Naito, Y, Ramsden, Z, Kassiotis, G, Dwornik, A, Karamani, A, Chain, B, Pearce, D, Karagianni, D, Galvez-Cancino, F, Stavrou, G, Mastrokalos, G, Lowe, H, Matos, I, Reading, J, Hartley, J, Selvaraju, K, Chen, K, Ensell, L, Shah, M, Litovchenko, M, Chervova, O, Pawlik, P, Hynds, R, Gamble, S, Ung, S, Bola, S, Spanswick, V, Wu, Y, Al-Sawaf, O, Jones, T, Beck, S, Tanic, M, Marafioti, T, Borg, E, Falzon, M, Khiroya, R, Toncheva, A, Abbosh, C, Richard, C, Naceur-Lombardelli, C, Gimeno-Valiente, F, Thakkar, K, Sunderland, M, Sivakumar, M, Kanu, N, Prymas, P, Saghafinia, S, Vanloo, S, Lam, J, Liu, W, Bunkum, A, Hessey, S, Zaccaria, S, Martinez-Ruiz, C, Black, J, Thol, K, Bentham, R, Litchfield, K, Mcgranahan, N, Quezada, S, Forster, M, Lee, S, Herrero, J, Nye, E, Stone, R, Nicod, J, Rane, J, Peggs, K, Ng, K, Dijkstra, K, Huska, M, Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Gorman, P, Stephens, R, Wong, Y, Kaplar, Z, Bandula, S, Watkins, T, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Swanton, C, Yuan, Y, Moore, D, Pan X., AbdulJabbar K., Coelho-Lima J., Grapa A. -I., Zhang H., Cheung A. H. K., Baena J., Karasaki T., Wilson C. R., Sereno M., Veeriah S., Aitken S. J., Hackshaw A., Nicholson A. G., Jamal-Hanjani M., Le Quesne J., Janes S. M., Hacker A. -M., Sharp A., Smith S., Dhanda H. K., Chan K., Pilotti C., Leslie R., Chuter D., MacKenzie M., Chee S., Alzetani A., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Kidd A., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Dick C., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Tufail M., Scotland M., Boyles R., Rathinam S., Fennell D. A., Wilson C., Marrone D., Dulloo S., Matharu G., Shaw J. A., Riley J., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Papadatos-Pastos D., Wilson J., Ahmad T., French J., Gilbert K., Naidu B., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Paiva-Correia A., Chaturvedi A., Priest L., Oliveira P., Gomes F., Brown K., Carter M., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Dive C., Aerts H. J. W. L., Schwarz R. F., Kaufmann T. L., Van Loo P., Wilson G. A., Rosenthal R., Rowan A., Bailey C., Lee C., Colliver E., Enfield K. S. S., Hill M. S., Angelova M., Pich O., Leung M., Frankell A. M., Hiley C. T., Lim E. L., Zhai H., Bakir M. A., Birkbak N. J., Lucas O., Huebner A., Puttick C., Grigoriadis K., Dietzen M., Biswas D., Athanasopoulou F., Ward S., Demeulemeester J., Castignani C., Cadieux E. L., Kisistok J., Sokac M., Szallasi Z., Diossy M., Salgado R., Stewart A., Magness A., Weeden C. E., Levi D., Gronroos E., Noorani I., Goldman J., Escudero M., Hobson P., Vendramin R., Boeing S., Denner T., Barbe V., Lu W. -T., Hill W., Naito Y., Ramsden Z., Kassiotis G., Dwornik A., Karamani A., Chain B., Pearce D. R., Karagianni D., Galvez-Cancino F., Stavrou G., Mastrokalos G., Lowe H. L., Matos I. G., Reading J. L., Hartley J. A., Selvaraju K., Chen K., Ensell L., Shah M., Litovchenko M., Chervova O., Pawlik P., Hynds R. E., Gamble S., Ung S. K. A., Bola S. K., Spanswick V., Wu Y., Al-Sawaf O., Jones T. P., Beck S., Tanic M., Marafioti T., Borg E., Falzon M., Khiroya R., Toncheva A., Abbosh C., Richard C., Naceur-Lombardelli C., Gimeno-Valiente F., Thakkar K., Sunderland M. W., Sivakumar M., Kanu N., Prymas P., Saghafinia S., Vanloo S., Lam J. M., Liu W. K., Bunkum A., Hessey S., Zaccaria S., Martinez-Ruiz C., Black J. R. M., Thol K., Bentham R., Litchfield K., McGranahan N., Quezada S. A., Forster M. D., Lee S. M., Herrero J., Nye E., Stone R. K., Nicod J., Rane J. K., Peggs K. S., Ng K. W., Dijkstra K., Huska M. R., Hoogenboom E. M., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Gorman P., Stephens R. C. M., Wong Y. N. S., Kaplar Z., Bandula S., Watkins T. B. K., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Swanton C., Yuan Y., and Moore D. A.
Abstract: The introduction of the International Association for the Study of Lung Cancer grading system has furthered interest in histopathological grading for risk stratification in lung adenocarcinoma. Complex morphology and high intratumoral heterogeneity present challenges to pathologists, prompting the development of artificial intelligence (AI) methods. Here we developed ANORAK (pyrAmid pooliNg crOss stReam Attention networK), encoding multiresolution inputs with an attention mechanism, to delineate growth patterns from hematoxylin and eosin-stained slides. In 1,372 lung adenocarcinomas across four independent cohorts, AI-based grading was prognostic of disease-free survival, and further assisted pathologists by consistently improving prognostication in stage I tumors. Tumors with discrepant patterns between AI and pathologists had notably higher intratumoral heterogeneity. Furthermore, ANORAK facilitates the morphological and spatial assessment of the acinar pattern, capturing acinus variations with pattern transition. Collectively, our AI method enabled the precision quantification and morphology investigation of growth patterns, reflecting intratumoral histological transitions in lung adenocarcinoma.
Published: 2024

3. Body composition and lung cancer-associated cachexia in TRACERx

Author: Al-Sawaf, O, Weiss, J, Skrzypski, M, Lam, J, Karasaki, T, Zambrana, F, Kidd, A, Frankell, A, Watkins, T, Martinez-Ruiz, C, Puttick, C, Black, J, Huebner, A, Bakir, M, Sokac, M, Collins, S, Veeriah, S, Magno, N, Naceur-Lombardelli, C, Prymas, P, Toncheva, A, Ward, S, Jayanth, N, Salgado, R, Bridge, C, Christiani, D, Mak, R, Bay, C, Rosenthal, M, Sattar, N, Welsh, P, Liu, Y, Perrimon, N, Popuri, K, Beg, M, Mcgranahan, N, Hackshaw, A, Breen, D, O'Rahilly, S, Birkbak, N, Aerts, H, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Shaw, J, Riley, J, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Gilbert, K, Naidu, B, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Gomes, F, Brown, K, Carter, M, Chaturvedi, A, Priest, L, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Kilgour, E, Dive, C, Schwarz, R, Kaufmann, T, Wilson, G, Rosenthal, R, Van Loo, P, Szallasi, Z, Kisistok, J, Diossy, M, Demeulemeester, J, Bunkum, A, Stewart, A, Magness, A, Rowan, A, Karamani, A, Chain, B, Campbell, B, Castignani, C, Bailey, C, Abbosh, C, Weeden, C, Lee, C, Richard, C, Hiley, C, Moore, D, Pearce, D, Karagianni, D, Biswas, D, Levi, D, Hoxha, E, Cadieux, E, Lim, E, Colliver, E, Nye, E, Gronroos, E, Galvez-Cancino, F, Athanasopoulou, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Zhai, H, Lowe, H, Matos, I, Goldman, J, Reading, J, Herrero, J, Rane, J, Nicod, J, Hartley, J, Peggs, K, Enfield, K, Selvaraju, K, Thol, K, Litchfield, K, Ng, K, Chen, K, Dijkstra, K, Grigoriadis, K, Thakkar, K, Ensell, L, Shah, M, Duran, M, Litovchenko, M, Sunderland, M, Hill, M, Dietzen, M, Leung, M, Escudero, M, Angelova, M, Tanic, M, Sivakumar, M, Kanu, N, Chervova, O, Lucas, O, Pich, O, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Hynds, R, Vendramin, R, Saghafinia, S, Lopez, S, Gamble, S, Ung, S, Quezada, S, Vanloo, S, Zaccaria, S, Hessey, S, Boeing, S, Beck, S, Bola, S, Denner, T, Marafioti, T, Mourikis, T, Spanswick, V, Barbe, V, Lu, W, Hill, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Clark, T, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Bandula, S, Sharp, A, Smith, S, Gower, N, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Scarlett, L, Richards, J, Ingram, P, Austin, S, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Nicholson, A, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Dick, C, Le Quesne, J, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Jamal-Hanjani, M, Swanton, C, Al-Sawaf O., Weiss J., Skrzypski M., Lam J. M., Karasaki T., Zambrana F., Kidd A. C., Frankell A. M., Watkins T. B. K., Martinez-Ruiz C., Puttick C., Black J. R. M., Huebner A., Bakir M. A., Sokac M., Collins S., Veeriah S., Magno N., Naceur-Lombardelli C., Prymas P., Toncheva A., Ward S., Jayanth N., Salgado R., Bridge C. P., Christiani D. C., Mak R. H., Bay C., Rosenthal M., Sattar N., Welsh P., Liu Y., Perrimon N., Popuri K., Beg M. F., McGranahan N., Hackshaw A., Breen D. M., O'Rahilly S., Birkbak N. J., Aerts H. J. W. L., Aerts H. J., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Shaw J. A., Riley J., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Gilbert K., Naidu B., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Gomes F., Brown K., Carter M., Chaturvedi A., Priest L., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Kilgour E., Dive C., Schwarz R. F., Kaufmann T. L., Wilson G. A., Rosenthal R., Van Loo P., Szallasi Z., Kisistok J., Diossy M., Demeulemeester J., Bunkum A., Stewart A., Magness A., Rowan A., Karamani A., Chain B., Campbell B. B., Castignani C., Bailey C., Abbosh C., Weeden C. E., Lee C., Richard C., Hiley C. T., Moore D. A., Pearce D. R., Karagianni D., Biswas D., Levi D., Hoxha E., Cadieux E. L., Lim E. L., Colliver E., Nye E., Gronroos E., Galvez-Cancino F., Athanasopoulou F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G., Zhai H., Lowe H. L., Matos I. G., Goldman J., Reading J. L., Herrero J., Rane J. K., Nicod J., Hartley J. A., Peggs K. S., Enfield K. S. S., Selvaraju K., Thol K., Litchfield K., Ng K. W., Chen K., Dijkstra K., Grigoriadis K., Thakkar K., Ensell L., Shah M., Duran M. V., Litovchenko M., Sunderland M. W., Hill M. S., Dietzen M., Leung M., Escudero M., Angelova M., Tanic M., Sivakumar M., Kanu N., Chervova O., Lucas O., Pich O., Hobson P., Pawlik P., Stone R. K., Bentham R., Hynds R. E., Vendramin R., Saghafinia S., Lopez S., Gamble S., Ung S. K. A., Quezada S. A., Vanloo S., Zaccaria S., Hessey S., Boeing S., Beck S., Bola S. K., Denner T., Marafioti T., Mourikis T. P., Spanswick V., Barbe V., Lu W. -T., Hill W., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Clark T., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Hoogenboom E. M., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Khiroya R., Stephens R. C., Wong Y. N. S., Bandula S., Sharp A., Smith S., Gower N., Dhanda H. K., Chan K., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Scarlett L., Richards J., Ingram P., Austin S., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Nicholson A. G., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Dick C., Le Quesne J., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Jamal-Hanjani M., Swanton C., Al-Sawaf, O, Weiss, J, Skrzypski, M, Lam, J, Karasaki, T, Zambrana, F, Kidd, A, Frankell, A, Watkins, T, Martinez-Ruiz, C, Puttick, C, Black, J, Huebner, A, Bakir, M, Sokac, M, Collins, S, Veeriah, S, Magno, N, Naceur-Lombardelli, C, Prymas, P, Toncheva, A, Ward, S, Jayanth, N, Salgado, R, Bridge, C, Christiani, D, Mak, R, Bay, C, Rosenthal, M, Sattar, N, Welsh, P, Liu, Y, Perrimon, N, Popuri, K, Beg, M, Mcgranahan, N, Hackshaw, A, Breen, D, O'Rahilly, S, Birkbak, N, Aerts, H, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Shaw, J, Riley, J, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Gilbert, K, Naidu, B, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Gomes, F, Brown, K, Carter, M, Chaturvedi, A, Priest, L, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Kilgour, E, Dive, C, Schwarz, R, Kaufmann, T, Wilson, G, Rosenthal, R, Van Loo, P, Szallasi, Z, Kisistok, J, Diossy, M, Demeulemeester, J, Bunkum, A, Stewart, A, Magness, A, Rowan, A, Karamani, A, Chain, B, Campbell, B, Castignani, C, Bailey, C, Abbosh, C, Weeden, C, Lee, C, Richard, C, Hiley, C, Moore, D, Pearce, D, Karagianni, D, Biswas, D, Levi, D, Hoxha, E, Cadieux, E, Lim, E, Colliver, E, Nye, E, Gronroos, E, Galvez-Cancino, F, Athanasopoulou, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Zhai, H, Lowe, H, Matos, I, Goldman, J, Reading, J, Herrero, J, Rane, J, Nicod, J, Hartley, J, Peggs, K, Enfield, K, Selvaraju, K, Thol, K, Litchfield, K, Ng, K, Chen, K, Dijkstra, K, Grigoriadis, K, Thakkar, K, Ensell, L, Shah, M, Duran, M, Litovchenko, M, Sunderland, M, Hill, M, Dietzen, M, Leung, M, Escudero, M, Angelova, M, Tanic, M, Sivakumar, M, Kanu, N, Chervova, O, Lucas, O, Pich, O, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Hynds, R, Vendramin, R, Saghafinia, S, Lopez, S, Gamble, S, Ung, S, Quezada, S, Vanloo, S, Zaccaria, S, Hessey, S, Boeing, S, Beck, S, Bola, S, Denner, T, Marafioti, T, Mourikis, T, Spanswick, V, Barbe, V, Lu, W, Hill, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Clark, T, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Bandula, S, Sharp, A, Smith, S, Gower, N, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Scarlett, L, Richards, J, Ingram, P, Austin, S, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Nicholson, A, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Dick, C, Le Quesne, J, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Jamal-Hanjani, M, Swanton, C, Al-Sawaf O., Weiss J., Skrzypski M., Lam J. M., Karasaki T., Zambrana F., Kidd A. C., Frankell A. M., Watkins T. B. K., Martinez-Ruiz C., Puttick C., Black J. R. M., Huebner A., Bakir M. A., Sokac M., Collins S., Veeriah S., Magno N., Naceur-Lombardelli C., Prymas P., Toncheva A., Ward S., Jayanth N., Salgado R., Bridge C. P., Christiani D. C., Mak R. H., Bay C., Rosenthal M., Sattar N., Welsh P., Liu Y., Perrimon N., Popuri K., Beg M. F., McGranahan N., Hackshaw A., Breen D. M., O'Rahilly S., Birkbak N. J., Aerts H. J. W. L., Aerts H. J., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Shaw J. A., Riley J., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Gilbert K., Naidu B., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Gomes F., Brown K., Carter M., Chaturvedi A., Priest L., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Kilgour E., Dive C., Schwarz R. F., Kaufmann T. L., Wilson G. A., Rosenthal R., Van Loo P., Szallasi Z., Kisistok J., Diossy M., Demeulemeester J., Bunkum A., Stewart A., Magness A., Rowan A., Karamani A., Chain B., Campbell B. B., Castignani C., Bailey C., Abbosh C., Weeden C. E., Lee C., Richard C., Hiley C. T., Moore D. A., Pearce D. R., Karagianni D., Biswas D., Levi D., Hoxha E., Cadieux E. L., Lim E. L., Colliver E., Nye E., Gronroos E., Galvez-Cancino F., Athanasopoulou F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G., Zhai H., Lowe H. L., Matos I. G., Goldman J., Reading J. L., Herrero J., Rane J. K., Nicod J., Hartley J. A., Peggs K. S., Enfield K. S. S., Selvaraju K., Thol K., Litchfield K., Ng K. W., Chen K., Dijkstra K., Grigoriadis K., Thakkar K., Ensell L., Shah M., Duran M. V., Litovchenko M., Sunderland M. W., Hill M. S., Dietzen M., Leung M., Escudero M., Angelova M., Tanic M., Sivakumar M., Kanu N., Chervova O., Lucas O., Pich O., Hobson P., Pawlik P., Stone R. K., Bentham R., Hynds R. E., Vendramin R., Saghafinia S., Lopez S., Gamble S., Ung S. K. A., Quezada S. A., Vanloo S., Zaccaria S., Hessey S., Boeing S., Beck S., Bola S. K., Denner T., Marafioti T., Mourikis T. P., Spanswick V., Barbe V., Lu W. -T., Hill W., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Clark T., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Hoogenboom E. M., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Khiroya R., Stephens R. C., Wong Y. N. S., Bandula S., Sharp A., Smith S., Gower N., Dhanda H. K., Chan K., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Scarlett L., Richards J., Ingram P., Austin S., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Nicholson A. G., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Dick C., Le Quesne J., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Jamal-Hanjani M., and Swanton C.
Abstract: Cancer-associated cachexia (CAC) is a major contributor to morbidity and mortality in individuals with non-small cell lung cancer. Key features of CAC include alterations in body composition and body weight. Here, we explore the association between body composition and body weight with survival and delineate potential biological processes and mediators that contribute to the development of CAC. Computed tomography-based body composition analysis of 651 individuals in the TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy (Rx)) study suggested that individuals in the bottom 20th percentile of the distribution of skeletal muscle or adipose tissue area at the time of lung cancer diagnosis, had significantly shorter lung cancer-specific survival and overall survival. This finding was validated in 420 individuals in the independent Boston Lung Cancer Study. Individuals classified as having developed CAC according to one or more features at relapse encompassing loss of adipose or muscle tissue, or body mass index-adjusted weight loss were found to have distinct tumor genomic and transcriptomic profiles compared with individuals who did not develop such features. Primary non-small cell lung cancers from individuals who developed CAC were characterized by enrichment of inflammatory signaling and epithelial–mesenchymal transitional pathways, and differentially expressed genes upregulated in these tumors included cancer-testis antigen MAGEA6 and matrix metalloproteinases, such as ADAMTS3. In an exploratory proteomic analysis of circulating putative mediators of cachexia performed in a subset of 110 individuals from TRACERx, a significant association between circulating GDF15 and loss of body weight, skeletal muscle and adipose tissue was identified at relapse, supporting the potential therapeutic relevance of targeting GDF15 in the management of CAC.
Published: 2023

4. Evolutionary characterization of lung adenocarcinoma morphology in TRACERx

Author: Karasaki, T, Moore, D, Veeriah, S, Naceur-Lombardelli, C, Toncheva, A, Magno, N, Ward, S, Bakir, M, Watkins, T, Grigoriadis, K, Huebner, A, Hill, M, Frankell, A, Abbosh, C, Puttick, C, Zhai, H, Gimeno-Valiente, F, Saghafinia, S, Kanu, N, Dietzen, M, Pich, O, Lim, E, Martinez-Ruiz, C, Black, J, Biswas, D, Campbell, B, Lee, C, Colliver, E, Enfield, K, Hessey, S, Hiley, C, Zaccaria, S, Litchfield, K, Birkbak, N, Cadieux, E, Demeulemeester, J, Van Loo, P, Adusumilli, P, Tan, K, Cheema, W, Sanchez-Vega, F, Jones, D, Rekhtman, N, Travis, W, Hackshaw, A, Marafioti, T, Salgado, R, Le Quesne, J, Nicholson, A, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Shaw, J, Riley, J, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Gilbert, K, Naidu, B, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Gomes, F, Brown, K, Carter, M, Chaturvedi, A, Priest, L, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Kilgour, E, Dive, C, Aerts, H, Schwarz, R, Kaufmann, T, Wilson, G, Rosenthal, R, Szallasi, Z, Kisistok, J, Sokac, M, Diossy, M, Bunkum, A, Stewart, A, Magness, A, Rowan, A, Karamani, A, Chain, B, Castignani, C, Bailey, C, Weeden, C, Richard, C, Pearce, D, Karagianni, D, Levi, D, Hoxha, E, Nye, E, Gronroos, E, Galvez-Cancino, F, Athanasopoulou, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Lowe, H, Matos, I, Goldman, J, Reading, J, Herrero, J, Rane, J, Nicod, J, Lam, J, Hartley, J, Peggs, K, Selvaraju, K, Thol, K, Ng, K, Chen, K, Dijkstra, K, Thakkar, K, Ensell, L, Shah, M, Duran, M, Litovchenko, M, Sunderland, M, Leung, M, Escudero, M, Angelova, M, Tanic, M, Sivakumar, M, Chervova, O, Lucas, O, Al-Sawaf, O, Prymas, P, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Hynds, R, Vendramin, R, Lopez, S, Gamble, S, Ung, S, Quezada, S, Vanloo, S, Boeing, S, Beck, S, Bola, S, Denner, T, Mourikis, T, Spanswick, V, Barbe, V, Lu, W, Hill, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Clark, T, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Bandula, S, Sharp, A, Smith, S, Gower, N, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Scarlett, L, Richards, J, Ingram, P, Austin, S, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Dick, C, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Mcgranahan, N, Swanton, C, Jamal-Hanjani, M, Karasaki T., Moore D. A., Veeriah S., Naceur-Lombardelli C., Toncheva A., Magno N., Ward S., Bakir M. A., Watkins T. B. K., Grigoriadis K., Huebner A., Hill M. S., Frankell A. M., Abbosh C., Puttick C., Zhai H., Gimeno-Valiente F., Saghafinia S., Kanu N., Dietzen M., Pich O., Lim E. L., Martinez-Ruiz C., Black J. R. M., Biswas D., Campbell B. B., Lee C., Colliver E., Enfield K. S. S., Hessey S., Hiley C. T., Zaccaria S., Litchfield K., Birkbak N. J., Cadieux E. L., Demeulemeester J., Van Loo P., Adusumilli P. S., Tan K. S., Cheema W., Sanchez-Vega F., Jones D. R., Rekhtman N., Travis W. D., Hackshaw A., Marafioti T., Salgado R., Le Quesne J., Nicholson A. G., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Shaw J. A., Riley J., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Gilbert K., Naidu B., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Gomes F., Brown K., Carter M., Chaturvedi A., Priest L., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Kilgour E., Dive C., Aerts H. J. W. L., Schwarz R. F., Kaufmann T. L., Wilson G. A., Rosenthal R., Szallasi Z., Kisistok J., Sokac M., Diossy M., Bunkum A., Stewart A., Magness A., Rowan A., Karamani A., Chain B., Castignani C., Bailey C., Weeden C. E., Richard C., Pearce D. R., Karagianni D., Levi D., Hoxha E., Nye E., Gronroos E., Galvez-Cancino F., Athanasopoulou F., Kassiotis G., Stavrou G., Mastrokalos G., Lowe H. L., Matos I. G., Goldman J., Reading J. L., Herrero J., Rane J. K., Nicod J., Lam J. M., Hartley J. A., Peggs K. S., Selvaraju K., Thol K., Ng K. W., Chen K., Dijkstra K., Thakkar K., Ensell L., Shah M., Duran M. V., Litovchenko M., Sunderland M. W., Leung M., Escudero M., Angelova M., Tanic M., Sivakumar M., Chervova O., Lucas O., Al-Sawaf O., Prymas P., Hobson P., Pawlik P., Stone R. K., Bentham R., Hynds R. E., Vendramin R., Lopez S., Gamble S., Ung S. K. A., Quezada S. A., Vanloo S., Boeing S., Beck S., Bola S. K., Denner T., Mourikis T. P., Spanswick V., Barbe V., Lu W. -T., Hill W., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Clark T., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Hoogenboom E. M., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Khiroya R., Stephens R. C., Wong Y. N. S., Bandula S., Sharp A., Smith S., Gower N., Dhanda H. K., Chan K., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Scarlett L., Richards J., Ingram P., Austin S., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Dick C., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., McGranahan N., Swanton C., Jamal-Hanjani M., Karasaki, T, Moore, D, Veeriah, S, Naceur-Lombardelli, C, Toncheva, A, Magno, N, Ward, S, Bakir, M, Watkins, T, Grigoriadis, K, Huebner, A, Hill, M, Frankell, A, Abbosh, C, Puttick, C, Zhai, H, Gimeno-Valiente, F, Saghafinia, S, Kanu, N, Dietzen, M, Pich, O, Lim, E, Martinez-Ruiz, C, Black, J, Biswas, D, Campbell, B, Lee, C, Colliver, E, Enfield, K, Hessey, S, Hiley, C, Zaccaria, S, Litchfield, K, Birkbak, N, Cadieux, E, Demeulemeester, J, Van Loo, P, Adusumilli, P, Tan, K, Cheema, W, Sanchez-Vega, F, Jones, D, Rekhtman, N, Travis, W, Hackshaw, A, Marafioti, T, Salgado, R, Le Quesne, J, Nicholson, A, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Shaw, J, Riley, J, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Gilbert, K, Naidu, B, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Gomes, F, Brown, K, Carter, M, Chaturvedi, A, Priest, L, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Kilgour, E, Dive, C, Aerts, H, Schwarz, R, Kaufmann, T, Wilson, G, Rosenthal, R, Szallasi, Z, Kisistok, J, Sokac, M, Diossy, M, Bunkum, A, Stewart, A, Magness, A, Rowan, A, Karamani, A, Chain, B, Castignani, C, Bailey, C, Weeden, C, Richard, C, Pearce, D, Karagianni, D, Levi, D, Hoxha, E, Nye, E, Gronroos, E, Galvez-Cancino, F, Athanasopoulou, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Lowe, H, Matos, I, Goldman, J, Reading, J, Herrero, J, Rane, J, Nicod, J, Lam, J, Hartley, J, Peggs, K, Selvaraju, K, Thol, K, Ng, K, Chen, K, Dijkstra, K, Thakkar, K, Ensell, L, Shah, M, Duran, M, Litovchenko, M, Sunderland, M, Leung, M, Escudero, M, Angelova, M, Tanic, M, Sivakumar, M, Chervova, O, Lucas, O, Al-Sawaf, O, Prymas, P, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Hynds, R, Vendramin, R, Lopez, S, Gamble, S, Ung, S, Quezada, S, Vanloo, S, Boeing, S, Beck, S, Bola, S, Denner, T, Mourikis, T, Spanswick, V, Barbe, V, Lu, W, Hill, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Clark, T, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Bandula, S, Sharp, A, Smith, S, Gower, N, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Scarlett, L, Richards, J, Ingram, P, Austin, S, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Dick, C, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Mcgranahan, N, Swanton, C, Jamal-Hanjani, M, Karasaki T., Moore D. A., Veeriah S., Naceur-Lombardelli C., Toncheva A., Magno N., Ward S., Bakir M. A., Watkins T. B. K., Grigoriadis K., Huebner A., Hill M. S., Frankell A. M., Abbosh C., Puttick C., Zhai H., Gimeno-Valiente F., Saghafinia S., Kanu N., Dietzen M., Pich O., Lim E. L., Martinez-Ruiz C., Black J. R. M., Biswas D., Campbell B. B., Lee C., Colliver E., Enfield K. S. S., Hessey S., Hiley C. T., Zaccaria S., Litchfield K., Birkbak N. J., Cadieux E. L., Demeulemeester J., Van Loo P., Adusumilli P. S., Tan K. S., Cheema W., Sanchez-Vega F., Jones D. R., Rekhtman N., Travis W. D., Hackshaw A., Marafioti T., Salgado R., Le Quesne J., Nicholson A. G., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Shaw J. A., Riley J., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Gilbert K., Naidu B., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Gomes F., Brown K., Carter M., Chaturvedi A., Priest L., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Kilgour E., Dive C., Aerts H. J. W. L., Schwarz R. F., Kaufmann T. L., Wilson G. A., Rosenthal R., Szallasi Z., Kisistok J., Sokac M., Diossy M., Bunkum A., Stewart A., Magness A., Rowan A., Karamani A., Chain B., Castignani C., Bailey C., Weeden C. E., Richard C., Pearce D. R., Karagianni D., Levi D., Hoxha E., Nye E., Gronroos E., Galvez-Cancino F., Athanasopoulou F., Kassiotis G., Stavrou G., Mastrokalos G., Lowe H. L., Matos I. G., Goldman J., Reading J. L., Herrero J., Rane J. K., Nicod J., Lam J. M., Hartley J. A., Peggs K. S., Selvaraju K., Thol K., Ng K. W., Chen K., Dijkstra K., Thakkar K., Ensell L., Shah M., Duran M. V., Litovchenko M., Sunderland M. W., Leung M., Escudero M., Angelova M., Tanic M., Sivakumar M., Chervova O., Lucas O., Al-Sawaf O., Prymas P., Hobson P., Pawlik P., Stone R. K., Bentham R., Hynds R. E., Vendramin R., Lopez S., Gamble S., Ung S. K. A., Quezada S. A., Vanloo S., Boeing S., Beck S., Bola S. K., Denner T., Mourikis T. P., Spanswick V., Barbe V., Lu W. -T., Hill W., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Clark T., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Hoogenboom E. M., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Khiroya R., Stephens R. C., Wong Y. N. S., Bandula S., Sharp A., Smith S., Gower N., Dhanda H. K., Chan K., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Scarlett L., Richards J., Ingram P., Austin S., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Dick C., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., McGranahan N., Swanton C., and Jamal-Hanjani M.
Abstract: Lung adenocarcinomas (LUADs) display a broad histological spectrum from low-grade lepidic tumors through to mid-grade acinar and papillary and high-grade solid, cribriform and micropapillary tumors. How morphology reflects tumor evolution and disease progression is poorly understood. Whole-exome sequencing data generated from 805 primary tumor regions and 121 paired metastatic samples across 248 LUADs from the TRACERx 421 cohort, together with RNA-sequencing data from 463 primary tumor regions, were integrated with detailed whole-tumor and regional histopathological analysis. Tumors with predominantly high-grade patterns showed increased chromosomal complexity, with higher burden of loss of heterozygosity and subclonal somatic copy number alterations. Individual regions in predominantly high-grade pattern tumors exhibited higher proliferation and lower clonal diversity, potentially reflecting large recent subclonal expansions. Co-occurrence of truncal loss of chromosomes 3p and 3q was enriched in predominantly low-/mid-grade tumors, while purely undifferentiated solid-pattern tumors had a higher frequency of truncal arm or focal 3q gains and SMARCA4 gene alterations compared with mixed-pattern tumors with a solid component, suggesting distinct evolutionary trajectories. Clonal evolution analysis revealed that tumors tend to evolve toward higher-grade patterns. The presence of micropapillary pattern and ‘tumor spread through air spaces’ were associated with intrathoracic recurrence, in contrast to the presence of solid/cribriform patterns, necrosis and preoperative circulating tumor DNA detection, which were associated with extra-thoracic recurrence. These data provide insights into the relationship between LUAD morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk.
Published: 2023

5. Genomic–transcriptomic evolution in lung cancer and metastasis

Author: Martinez-Ruiz, C, Black, J, Puttick, C, Hill, M, Demeulemeester, J, Larose Cadieux, E, Thol, K, Jones, T, Veeriah, S, Naceur-Lombardelli, C, Toncheva, A, Prymas, P, Rowan, A, Ward, S, Cubitt, L, Athanasopoulou, F, Pich, O, Karasaki, T, Moore, D, Salgado, R, Colliver, E, Castignani, C, Dietzen, M, Huebner, A, Al Bakir, M, Tanic, M, Watkins, T, Lim, E, Al-Rashed, A, Lang, D, Clements, J, Cook, D, Rosenthal, R, Wilson, G, Frankell, A, de Carne Trecesson, S, East, P, Kanu, N, Litchfield, K, Birkbak, N, Hackshaw, A, Beck, S, Van Loo, P, Jamal-Hanjani, M, Mcgranahan, N, Swanton, C, Bakir, M, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Shaw, J, Riley, J, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Gilbert, K, Naidu, B, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Gomes, F, Brown, K, Carter, M, Chaturvedi, A, Priest, L, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Kilgour, E, Dive, C, Aerts, H, Schwarz, R, Kaufmann, T, Szallasi, Z, Kisistok, J, Sokac, M, Diossy, M, Bunkum, A, Stewart, A, Magness, A, Karamani, A, Chain, B, Campbell, B, Bailey, C, Abbosh, C, Weeden, C, Lee, C, Richard, C, Hiley, C, Pearce, D, Karagianni, D, Biswas, D, Levi, D, Hoxha, E, Nye, E, Gronroos, E, Galvez-Cancino, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Zhai, H, Lowe, H, Matos, I, Goldman, J, Reading, J, Herrero, J, Rane, J, Nicod, J, Lam, J, Hartley, J, Peggs, K, Enfield, K, Selvaraju, K, Ng, K, Chen, K, Dijkstra, K, Grigoriadis, K, Thakkar, K, Ensell, L, Shah, M, Duran, M, Litovchenko, M, Sunderland, M, Leung, M, Escudero, M, Angelova, M, Sivakumar, M, Chervova, O, Lucas, O, Al-Sawaf, O, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Hynds, R, Vendramin, R, Saghafinia, S, Lopez, S, Gamble, S, Ung, S, Quezada, S, Vanloo, S, Zaccaria, S, Hessey, S, Boeing, S, Bola, S, Denner, T, Marafioti, T, Mourikis, T, Spanswick, V, Barbe, V, Lu, W, Hill, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Clark, T, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Bandula, S, Sharp, A, Smith, S, Gower, N, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Scarlett, L, Richards, J, Ingram, P, Austin, S, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Nicholson, A, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Dick, C, Le Quesne, J, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Martinez-Ruiz C., Black J. R. M., Puttick C., Hill M. S., Demeulemeester J., Larose Cadieux E., Thol K., Jones T. P., Veeriah S., Naceur-Lombardelli C., Toncheva A., Prymas P., Rowan A., Ward S., Cubitt L., Athanasopoulou F., Pich O., Karasaki T., Moore D. A., Salgado R., Colliver E., Castignani C., Dietzen M., Huebner A., Al Bakir M., Tanic M., Watkins T. B. K., Lim E. L., Al-Rashed A. M., Lang D., Clements J., Cook D. E., Rosenthal R., Wilson G. A., Frankell A. M., de Carne Trecesson S., East P., Kanu N., Litchfield K., Birkbak N. J., Hackshaw A., Beck S., Van Loo P., Jamal-Hanjani M., McGranahan N., Swanton C., Bakir M. A., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Shaw J. A., Riley J., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Gilbert K., Naidu B., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Gomes F., Brown K., Carter M., Chaturvedi A., Priest L., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Kilgour E., Dive C., Aerts H. J. W. L., Schwarz R. F., Kaufmann T. L., Szallasi Z., Kisistok J., Sokac M., Diossy M., Bunkum A., Stewart A., Magness A., Karamani A., Chain B., Campbell B. B., Bailey C., Abbosh C., Weeden C. E., Lee C., Richard C., Hiley C. T., Pearce D. R., Karagianni D., Biswas D., Levi D., Hoxha E., Nye E., Gronroos E., Galvez-Cancino F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G., Zhai H., Lowe H. L., Matos I. G., Goldman J., Reading J. L., Herrero J., Rane J. K., Nicod J., Lam J. M., Hartley J. A., Peggs K. S., Enfield K. S. S., Selvaraju K., Ng K. W., Chen K., Dijkstra K., Grigoriadis K., Thakkar K., Ensell L., Shah M., Duran M. V., Litovchenko M., Sunderland M. W., Leung M., Escudero M., Angelova M., Sivakumar M., Chervova O., Lucas O., Al-Sawaf O., Hobson P., Pawlik P., Stone R. K., Bentham R., Hynds R. E., Vendramin R., Saghafinia S., Lopez S., Gamble S., Ung S. K. A., Quezada S. A., Vanloo S., Zaccaria S., Hessey S., Boeing S., Bola S. K., Denner T., Marafioti T., Mourikis T. P., Spanswick V., Barbe V., Lu W. -T., Hill W., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Clark T., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Hoogenboom E. M., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Khiroya R., Stephens R. C. M., Wong Y. N. S., Bandula S., Sharp A., Smith S., Gower N., Dhanda H. K., Chan K., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Scarlett L., Richards J., Ingram P., Austin S., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Nicholson A. G., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Dick C., Le Quesne J., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Martinez-Ruiz, C, Black, J, Puttick, C, Hill, M, Demeulemeester, J, Larose Cadieux, E, Thol, K, Jones, T, Veeriah, S, Naceur-Lombardelli, C, Toncheva, A, Prymas, P, Rowan, A, Ward, S, Cubitt, L, Athanasopoulou, F, Pich, O, Karasaki, T, Moore, D, Salgado, R, Colliver, E, Castignani, C, Dietzen, M, Huebner, A, Al Bakir, M, Tanic, M, Watkins, T, Lim, E, Al-Rashed, A, Lang, D, Clements, J, Cook, D, Rosenthal, R, Wilson, G, Frankell, A, de Carne Trecesson, S, East, P, Kanu, N, Litchfield, K, Birkbak, N, Hackshaw, A, Beck, S, Van Loo, P, Jamal-Hanjani, M, Mcgranahan, N, Swanton, C, Bakir, M, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Shaw, J, Riley, J, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Gilbert, K, Naidu, B, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Gomes, F, Brown, K, Carter, M, Chaturvedi, A, Priest, L, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Kilgour, E, Dive, C, Aerts, H, Schwarz, R, Kaufmann, T, Szallasi, Z, Kisistok, J, Sokac, M, Diossy, M, Bunkum, A, Stewart, A, Magness, A, Karamani, A, Chain, B, Campbell, B, Bailey, C, Abbosh, C, Weeden, C, Lee, C, Richard, C, Hiley, C, Pearce, D, Karagianni, D, Biswas, D, Levi, D, Hoxha, E, Nye, E, Gronroos, E, Galvez-Cancino, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Zhai, H, Lowe, H, Matos, I, Goldman, J, Reading, J, Herrero, J, Rane, J, Nicod, J, Lam, J, Hartley, J, Peggs, K, Enfield, K, Selvaraju, K, Ng, K, Chen, K, Dijkstra, K, Grigoriadis, K, Thakkar, K, Ensell, L, Shah, M, Duran, M, Litovchenko, M, Sunderland, M, Leung, M, Escudero, M, Angelova, M, Sivakumar, M, Chervova, O, Lucas, O, Al-Sawaf, O, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Hynds, R, Vendramin, R, Saghafinia, S, Lopez, S, Gamble, S, Ung, S, Quezada, S, Vanloo, S, Zaccaria, S, Hessey, S, Boeing, S, Bola, S, Denner, T, Marafioti, T, Mourikis, T, Spanswick, V, Barbe, V, Lu, W, Hill, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Clark, T, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Bandula, S, Sharp, A, Smith, S, Gower, N, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Scarlett, L, Richards, J, Ingram, P, Austin, S, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Nicholson, A, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Dick, C, Le Quesne, J, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Martinez-Ruiz C., Black J. R. M., Puttick C., Hill M. S., Demeulemeester J., Larose Cadieux E., Thol K., Jones T. P., Veeriah S., Naceur-Lombardelli C., Toncheva A., Prymas P., Rowan A., Ward S., Cubitt L., Athanasopoulou F., Pich O., Karasaki T., Moore D. A., Salgado R., Colliver E., Castignani C., Dietzen M., Huebner A., Al Bakir M., Tanic M., Watkins T. B. K., Lim E. L., Al-Rashed A. M., Lang D., Clements J., Cook D. E., Rosenthal R., Wilson G. A., Frankell A. M., de Carne Trecesson S., East P., Kanu N., Litchfield K., Birkbak N. J., Hackshaw A., Beck S., Van Loo P., Jamal-Hanjani M., McGranahan N., Swanton C., Bakir M. A., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Shaw J. A., Riley J., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Gilbert K., Naidu B., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Gomes F., Brown K., Carter M., Chaturvedi A., Priest L., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Kilgour E., Dive C., Aerts H. J. W. L., Schwarz R. F., Kaufmann T. L., Szallasi Z., Kisistok J., Sokac M., Diossy M., Bunkum A., Stewart A., Magness A., Karamani A., Chain B., Campbell B. B., Bailey C., Abbosh C., Weeden C. E., Lee C., Richard C., Hiley C. T., Pearce D. R., Karagianni D., Biswas D., Levi D., Hoxha E., Nye E., Gronroos E., Galvez-Cancino F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G., Zhai H., Lowe H. L., Matos I. G., Goldman J., Reading J. L., Herrero J., Rane J. K., Nicod J., Lam J. M., Hartley J. A., Peggs K. S., Enfield K. S. S., Selvaraju K., Ng K. W., Chen K., Dijkstra K., Grigoriadis K., Thakkar K., Ensell L., Shah M., Duran M. V., Litovchenko M., Sunderland M. W., Leung M., Escudero M., Angelova M., Sivakumar M., Chervova O., Lucas O., Al-Sawaf O., Hobson P., Pawlik P., Stone R. K., Bentham R., Hynds R. E., Vendramin R., Saghafinia S., Lopez S., Gamble S., Ung S. K. A., Quezada S. A., Vanloo S., Zaccaria S., Hessey S., Boeing S., Bola S. K., Denner T., Marafioti T., Mourikis T. P., Spanswick V., Barbe V., Lu W. -T., Hill W., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Clark T., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Hoogenboom E. M., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Khiroya R., Stephens R. C. M., Wong Y. N. S., Bandula S., Sharp A., Smith S., Gower N., Dhanda H. K., Chan K., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Scarlett L., Richards J., Ingram P., Austin S., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Nicholson A. G., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Dick C., Le Quesne J., Kirk A., Asif M., Bilancia R., Kostoulas N., and Thomas M.
Abstract: Intratumour heterogeneity (ITH) fuels lung cancer evolution, which leads to immune evasion and resistance to therapy1. Here, using paired whole-exome and RNA sequencing data, we investigate intratumour transcriptomic diversity in 354 non-small cell lung cancer tumours from 347 out of the first 421 patients prospectively recruited into the TRACERx study2,3. Analyses of 947 tumour regions, representing both primary and metastatic disease, alongside 96 tumour-adjacent normal tissue samples implicate the transcriptome as a major source of phenotypic variation. Gene expression levels and ITH relate to patterns of positive and negative selection during tumour evolution. We observe frequent copy number-independent allele-specific expression that is linked to epigenomic dysfunction. Allele-specific expression can also result in genomic–transcriptomic parallel evolution, which converges on cancer gene disruption. We extract signatures of RNA single-base substitutions and link their aetiology to the activity of the RNA-editing enzymes ADAR and APOBEC3A, thereby revealing otherwise undetected ongoing APOBEC activity in tumours. Characterizing the transcriptomes of primary–metastatic tumour pairs, we combine multiple machine-learning approaches that leverage genomic and transcriptomic variables to link metastasis-seeding potential to the evolutionary context of mutations and increased proliferation within primary tumour regions. These results highlight the interplay between the genome and transcriptome in influencing ITH, lung cancer evolution and metastasis.
Published: 2023

6. Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA

Author: Abbosh, C, Frankell, A, Harrison, T, Kisistok, J, Garnett, A, Johnson, L, Veeriah, S, Moreau, M, Chesh, A, Chaunzwa, T, Weiss, J, Schroeder, M, Ward, S, Grigoriadis, K, Shahpurwalla, A, Litchfield, K, Puttick, C, Biswas, D, Karasaki, T, Black, J, Martinez-Ruiz, C, Bakir, M, Pich, O, Watkins, T, Lim, E, Huebner, A, Moore, D, Godin-Heymann, N, L'Hernault, A, Bye, H, Odell, A, Roberts, P, Gomes, F, Patel, A, Manzano, E, Hiley, C, Carey, N, Riley, J, Cook, D, Hodgson, D, Stetson, D, Barrett, J, Kortlever, R, Evan, G, Hackshaw, A, Daber, R, Shaw, J, Aerts, H, Licon, A, Stahl, J, Jamal-Hanjani, M, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Gilbert, K, Naidu, B, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Brown, K, Carter, M, Chaturvedi, A, Priest, L, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Kilgour, E, Dive, C, Schwarz, R, Kaufmann, T, Wilson, G, Rosenthal, R, Van Loo, P, Szallasi, Z, Sokac, M, Salgado, R, Diossy, M, Demeulemeester, J, Bunkum, A, Stewart, A, Magness, A, Rowan, A, Karamani, A, Toncheva, A, Chain, B, Campbell, B, Castignani, C, Bailey, C, Weeden, C, Lee, C, Richard, C, Naceur-Lombardelli, C, Pearce, D, Karagianni, D, Levi, D, Hoxha, E, Larose Cadieux, E, Colliver, E, Nye, E, Gronroos, E, Galvez-Cancino, F, Athanasopoulou, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Zhai, H, Lowe, H, Matos, I, Goldman, J, Reading, J, Herrero, J, Rane, J, Nicod, J, Lam, J, Hartley, J, Peggs, K, Enfield, K, Selvaraju, K, Thol, K, Ng, K, Chen, K, Dijkstra, K, Thakkar, K, Ensell, L, Shah, M, Vasquez, M, Litovchenko, M, Werner Sunderland, M, Hill, M, Dietzen, M, Leung, M, Escudero, M, Angelova, M, Tanic, M, Sivakumar, M, Kanu, N, Chervova, O, Lucas, O, Al-Sawaf, O, Prymas, P, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Hynds, R, Vendramin, R, Saghafinia, S, Lopez, S, Gamble, S, Ung, S, Quezada, S, Vanloo, S, Zaccaria, S, Hessey, S, Boeing, S, Beck, S, Bola, S, Denner, T, Marafioti, T, Mourikis, T, Spanswick, V, Barbe, V, Lu, W, Hill, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Clark, T, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Martinoni Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Bandula, S, Sharp, A, Smith, S, Gower, N, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Scarlett, L, Richards, J, Ingram, P, Austin, S, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Nicholson, A, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Dick, C, Le Quesne, J, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Birkbak, N, Mcgranahan, N, Swanton, C, Abbosh C., Frankell A. M., Harrison T., Kisistok J., Garnett A., Johnson L., Veeriah S., Moreau M., Chesh A., Chaunzwa T. L., Weiss J., Schroeder M. R., Ward S., Grigoriadis K., Shahpurwalla A., Litchfield K., Puttick C., Biswas D., Karasaki T., Black J. R. M., Martinez-Ruiz C., Bakir M. A., Pich O., Watkins T. B. K., Lim E. L., Huebner A., Moore D. A., Godin-Heymann N., L'Hernault A., Bye H., Odell A., Roberts P., Gomes F., Patel A. J., Manzano E., Hiley C. T., Carey N., Riley J., Cook D. E., Hodgson D., Stetson D., Barrett J. C., Kortlever R. M., Evan G. I., Hackshaw A., Daber R. D., Shaw J. A., Aerts H. J. W. L., Licon A., Stahl J., Jamal-Hanjani M., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Gilbert K., Naidu B., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Brown K., Carter M., Chaturvedi A., Priest L., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Kilgour E., Dive C., Schwarz R. F., Kaufmann T. L., Wilson G. A., Rosenthal R., Van Loo P., Szallasi Z., Sokac M., Salgado R., Diossy M., Demeulemeester J., Bunkum A., Stewart A., Magness A., Rowan A., Karamani A., Toncheva A., Chain B., Campbell B. B., Castignani C., Bailey C., Weeden C. E., Lee C., Richard C., Naceur-Lombardelli C., Pearce D. R., Karagianni D., Levi D., Hoxha E., Larose Cadieux E., Colliver E., Nye E., Gronroos E., Galvez-Cancino F., Athanasopoulou F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G., Zhai H., Lowe H. L., Matos I., Goldman J., Reading J. L., Herrero J., Rane J. K., Nicod J., Lam J. M., Hartley J. A., Peggs K. S., Enfield K. S. S., Selvaraju K., Thol K., Ng K. W., Chen K., Dijkstra K., Thakkar K., Ensell L., Shah M., Vasquez M., Litovchenko M., Werner Sunderland M., Hill M. S., Dietzen M., Leung M., Escudero M., Angelova M., Tanic M., Sivakumar M., Kanu N., Chervova O., Lucas O., Al-Sawaf O., Prymas P., Hobson P., Pawlik P., Stone R. K., Bentham R., Hynds R. E., Vendramin R., Saghafinia S., Lopez S., Gamble S., Ung S. K. A., Quezada S. A., Vanloo S., Zaccaria S., Hessey S., Boeing S., Beck S., Bola S. K., Denner T., Marafioti T., Mourikis T. P., Spanswick V., Barbe V., Lu W. -T., Hill W., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Clark T., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Martinoni Hoogenboom E., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Khiroya R., Stephens R. C., Wong Y. N. S., Bandula S., Sharp A., Smith S., Gower N., Dhanda H. K., Chan K., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Scarlett L., Richards J., Ingram P., Austin S., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Nicholson A. G., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Dick C., Le Quesne J., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Birkbak N. J., McGranahan N., Swanton C., Abbosh, C, Frankell, A, Harrison, T, Kisistok, J, Garnett, A, Johnson, L, Veeriah, S, Moreau, M, Chesh, A, Chaunzwa, T, Weiss, J, Schroeder, M, Ward, S, Grigoriadis, K, Shahpurwalla, A, Litchfield, K, Puttick, C, Biswas, D, Karasaki, T, Black, J, Martinez-Ruiz, C, Bakir, M, Pich, O, Watkins, T, Lim, E, Huebner, A, Moore, D, Godin-Heymann, N, L'Hernault, A, Bye, H, Odell, A, Roberts, P, Gomes, F, Patel, A, Manzano, E, Hiley, C, Carey, N, Riley, J, Cook, D, Hodgson, D, Stetson, D, Barrett, J, Kortlever, R, Evan, G, Hackshaw, A, Daber, R, Shaw, J, Aerts, H, Licon, A, Stahl, J, Jamal-Hanjani, M, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Gilbert, K, Naidu, B, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Brown, K, Carter, M, Chaturvedi, A, Priest, L, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Kilgour, E, Dive, C, Schwarz, R, Kaufmann, T, Wilson, G, Rosenthal, R, Van Loo, P, Szallasi, Z, Sokac, M, Salgado, R, Diossy, M, Demeulemeester, J, Bunkum, A, Stewart, A, Magness, A, Rowan, A, Karamani, A, Toncheva, A, Chain, B, Campbell, B, Castignani, C, Bailey, C, Weeden, C, Lee, C, Richard, C, Naceur-Lombardelli, C, Pearce, D, Karagianni, D, Levi, D, Hoxha, E, Larose Cadieux, E, Colliver, E, Nye, E, Gronroos, E, Galvez-Cancino, F, Athanasopoulou, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Zhai, H, Lowe, H, Matos, I, Goldman, J, Reading, J, Herrero, J, Rane, J, Nicod, J, Lam, J, Hartley, J, Peggs, K, Enfield, K, Selvaraju, K, Thol, K, Ng, K, Chen, K, Dijkstra, K, Thakkar, K, Ensell, L, Shah, M, Vasquez, M, Litovchenko, M, Werner Sunderland, M, Hill, M, Dietzen, M, Leung, M, Escudero, M, Angelova, M, Tanic, M, Sivakumar, M, Kanu, N, Chervova, O, Lucas, O, Al-Sawaf, O, Prymas, P, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Hynds, R, Vendramin, R, Saghafinia, S, Lopez, S, Gamble, S, Ung, S, Quezada, S, Vanloo, S, Zaccaria, S, Hessey, S, Boeing, S, Beck, S, Bola, S, Denner, T, Marafioti, T, Mourikis, T, Spanswick, V, Barbe, V, Lu, W, Hill, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Clark, T, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Martinoni Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Bandula, S, Sharp, A, Smith, S, Gower, N, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Scarlett, L, Richards, J, Ingram, P, Austin, S, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Nicholson, A, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Dick, C, Le Quesne, J, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Birkbak, N, Mcgranahan, N, Swanton, C, Abbosh C., Frankell A. M., Harrison T., Kisistok J., Garnett A., Johnson L., Veeriah S., Moreau M., Chesh A., Chaunzwa T. L., Weiss J., Schroeder M. R., Ward S., Grigoriadis K., Shahpurwalla A., Litchfield K., Puttick C., Biswas D., Karasaki T., Black J. R. M., Martinez-Ruiz C., Bakir M. A., Pich O., Watkins T. B. K., Lim E. L., Huebner A., Moore D. A., Godin-Heymann N., L'Hernault A., Bye H., Odell A., Roberts P., Gomes F., Patel A. J., Manzano E., Hiley C. T., Carey N., Riley J., Cook D. E., Hodgson D., Stetson D., Barrett J. C., Kortlever R. M., Evan G. I., Hackshaw A., Daber R. D., Shaw J. A., Aerts H. J. W. L., Licon A., Stahl J., Jamal-Hanjani M., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Gilbert K., Naidu B., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Brown K., Carter M., Chaturvedi A., Priest L., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Kilgour E., Dive C., Schwarz R. F., Kaufmann T. L., Wilson G. A., Rosenthal R., Van Loo P., Szallasi Z., Sokac M., Salgado R., Diossy M., Demeulemeester J., Bunkum A., Stewart A., Magness A., Rowan A., Karamani A., Toncheva A., Chain B., Campbell B. B., Castignani C., Bailey C., Weeden C. E., Lee C., Richard C., Naceur-Lombardelli C., Pearce D. R., Karagianni D., Levi D., Hoxha E., Larose Cadieux E., Colliver E., Nye E., Gronroos E., Galvez-Cancino F., Athanasopoulou F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G., Zhai H., Lowe H. L., Matos I., Goldman J., Reading J. L., Herrero J., Rane J. K., Nicod J., Lam J. M., Hartley J. A., Peggs K. S., Enfield K. S. S., Selvaraju K., Thol K., Ng K. W., Chen K., Dijkstra K., Thakkar K., Ensell L., Shah M., Vasquez M., Litovchenko M., Werner Sunderland M., Hill M. S., Dietzen M., Leung M., Escudero M., Angelova M., Tanic M., Sivakumar M., Kanu N., Chervova O., Lucas O., Al-Sawaf O., Prymas P., Hobson P., Pawlik P., Stone R. K., Bentham R., Hynds R. E., Vendramin R., Saghafinia S., Lopez S., Gamble S., Ung S. K. A., Quezada S. A., Vanloo S., Zaccaria S., Hessey S., Boeing S., Beck S., Bola S. K., Denner T., Marafioti T., Mourikis T. P., Spanswick V., Barbe V., Lu W. -T., Hill W., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Clark T., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Martinoni Hoogenboom E., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Khiroya R., Stephens R. C., Wong Y. N. S., Bandula S., Sharp A., Smith S., Gower N., Dhanda H. K., Chan K., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Scarlett L., Richards J., Ingram P., Austin S., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Nicholson A. G., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Dick C., Le Quesne J., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Birkbak N. J., McGranahan N., and Swanton C.
Abstract: Circulating tumour DNA (ctDNA) can be used to detect and profile residual tumour cells persisting after curative intent therapy1. The study of large patient cohorts incorporating longitudinal plasma sampling and extended follow-up is required to determine the role of ctDNA as a phylogenetic biomarker of relapse in early-stage non-small-cell lung cancer (NSCLC). Here we developed ctDNA methods tracking a median of 200 mutations identified in resected NSCLC tissue across 1,069 plasma samples collected from 197 patients enrolled in the TRACERx study2. A lack of preoperative ctDNA detection distinguished biologically indolent lung adenocarcinoma with good clinical outcome. Postoperative plasma analyses were interpreted within the context of standard-of-care radiological surveillance and administration of cytotoxic adjuvant therapy. Landmark analyses of plasma samples collected within 120 days after surgery revealed ctDNA detection in 25% of patients, including 49% of all patients who experienced clinical relapse; 3 to 6 monthly ctDNA surveillance identified impending disease relapse in an additional 20% of landmark-negative patients. We developed a bioinformatic tool (ECLIPSE) for non-invasive tracking of subclonal architecture at low ctDNA levels. ECLIPSE identified patients with polyclonal metastatic dissemination, which was associated with a poor clinical outcome. By measuring subclone cancer cell fractions in preoperative plasma, we found that subclones seeding future metastases were significantly more expanded compared with non-metastatic subclones. Our findings will support (neo)adjuvant trial advances and provide insights into the process of metastatic dissemination using low-ctDNA-level liquid biopsy.
Published: 2023

7. Antibodies against endogenous retroviruses promote lung cancer immunotherapy

Author: Ng, K, Boumelha, J, Enfield, K, Almagro, J, Cha, H, Pich, O, Karasaki, T, Moore, D, Salgado, R, Sivakumar, M, Young, G, Molina-Arcas, M, de Carne Trecesson, S, Anastasiou, P, Fendler, A, Au, L, Shepherd, S, Martinez-Ruiz, C, Puttick, C, Black, J, Watkins, T, Kim, H, Shim, S, Faulkner, N, Attig, J, Veeriah, S, Magno, N, Ward, S, Frankell, A, Al Bakir, M, Lim, E, Hill, M, Wilson, G, Cook, D, Birkbak, N, Behrens, A, Yousaf, N, Popat, S, Hackshaw, A, Rowan, A, Huebner, A, Campbell, B, Bailey, C, Lee, C, Biswas, D, Colliver, E, Athanasopoulou, F, Zhai, H, Rane, J, Grigoriadis, K, Dietzen, M, Leung, M, Angelova, M, Lucas, O, Al-Sawaf, O, Rosenthal, R, Nicod, J, Bunkum, A, Toncheva, A, Abbosh, C, Richard, C, Naceur-Lombardelli, C, Gimeno-Valiente, F, Lam, J, Thol, K, Thakkar, K, Werner Sunderland, M, Forster, M, Kanu, N, Prymas, P, Bentham, R, Saghafinia, S, Quezada, S, Vanloo, S, Zaccaria, S, Lee, S, Hessey, S, Liu, W, Papadatos-Pastos, D, Wilson, J, Benafif, S, Ahmad, T, Borg, E, Falzon, M, Khiroya, R, Marafioti, T, Sharp, A, Pilotti, C, Dhanda, H, Chan, K, Gower, N, Leslie, R, Smith, S, Nicholson, A, Herrero, J, Castignani, C, Larose Cadieux, E, Demeulemeester, J, Van Loo, P, Peggs, K, Veiga, C, Royle, G, Collins-Fekete, C, Procter, A, Nair, A, Ahmed, A, Taylor, M, Navani, N, Thakrar, R, Lawrence, D, Patrini, D, Nye, E, Stone, R, Chuter, D, Mackenzie, M, Fraioli, F, Ashford, P, Janes, S, Tanic, M, Beck, S, Rice, A, Devaraj, A, Proli, C, Kaniu, D, Bhayani, H, Chavan, H, Raubenheimer, H, Ambrose, L, Malima, M, Fernandes, N, De Sousa, P, Shah, P, Booth, S, Buderi, S, Jordan, S, Begum, S, Boleti, E, Stewart, A, Magness, A, Weeden, C, Levi, D, Gronroos, E, Goldman, J, Escudero, M, Hobson, P, Vendramin, R, Boeing, S, Denner, T, Barbe, V, Lu, W, Hill, W, Naito, Y, Ramsden, Z, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Gilbert, K, Karamani, A, Chain, B, Pearce, D, Karagianni, D, Hoxha, E, Galvez-Cancino, F, Stavrou, G, Mastrokalos, G, Lowe, H, Matos, I, Reading, J, Hartley, J, Selvaraju, K, Chen, K, Ensell, L, Shah, M, Vasquez, M, Litovchenko, M, Chervova, O, Pawlik, P, Hynds, R, Lopez, S, Gamble, S, Ung, S, Bola, S, Mourikis, T, Spanswick, V, Wu, Y, Martinoni Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Stephens, R, Bandula, S, Wong, Y, Clark, T, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Naidu, B, Matharu, G, Shaw, J, Riley, J, Primrose, L, Le Quesne, J, Blyth, K, Kerr, A, Clipson, A, Chaturvedi, A, Dive, C, Rothwell, D, Kilgour, E, Tugwood, J, Priest, L, Oliveira, P, Crosbie, P, Price, G, Cave, J, Kerr, K, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Kirk, A, Thomas, M, Asif, M, Kostoulas, N, Bilancia, R, Middleton, G, Shackcloth, M, Leek, A, Hodgkinson, J, Totten, N, Dick, C, Robinson, L, Russell, P, Hewish, M, Danson, S, Lester, J, Gomes, F, Brown, K, Carter, M, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Alzetani, A, Richards, J, Scarlett, L, Ingram, P, Chee, S, Austin, S, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Fennell, D, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Aerts, H, Kaufmann, T, Schwarz, R, Kisistok, J, Sokac, M, Diossy, M, Szallasi, Z, Dijkstra, K, Yuan, Y, Byrne, F, Boos, L, Shum, B, Gerard, C, Schmitt, A, Messiou, C, Cunningham, D, Chau, I, Starling, N, Turner, N, Welsh, L, Jones, R, Droney, J, Banerjee, S, Tatham, K, Jhanji, S, Harrington, K, Okines, A, Reid, A, Young, K, Furness, A, Pickering, L, Nicholson, E, Kumar, S, Wilkinson, K, Swerdlow, A, Wilkinson, R, Hiley, C, Litchfield, K, Mcgranahan, N, Jamal-Hanjani, M, Larkin, J, Turajlic, S, Swanton, C, Downward, J, Kassiotis, G, Ng K. W., Boumelha J., Enfield K. S. S., Almagro J., Cha H., Pich O., Karasaki T., Moore D. A., Salgado R., Sivakumar M., Young G., Molina-Arcas M., de Carne Trecesson S., Anastasiou P., Fendler A., Au L., Shepherd S. T. C., Martinez-Ruiz C., Puttick C., Black J. R. M., Watkins T. B. K., Kim H., Shim S., Faulkner N., Attig J., Veeriah S., Magno N., Ward S., Frankell A. M., Al Bakir M., Lim E. L., Hill M. S., Wilson G. A., Cook D. E., Birkbak N. J., Behrens A., Yousaf N., Popat S., Hackshaw A., Rowan A., Huebner A., Campbell B. B., Bailey C., Lee C., Biswas D., Colliver E., Athanasopoulou F., Zhai H., Rane J. K., Grigoriadis K., Dietzen M., Leung M., Angelova M., Lucas O., Al-Sawaf O., Rosenthal R., Nicod J., Bunkum A., Toncheva A., Abbosh C., Richard C., Naceur-Lombardelli C., Gimeno-Valiente F., Lam J. M., Thol K., Thakkar K., Werner Sunderland M., Forster M. D., Kanu N., Prymas P., Bentham R., Saghafinia S., Quezada S. A., Vanloo S., Zaccaria S., Lee S. M., Hessey S., Liu W. K., Papadatos-Pastos D., Wilson J., Benafif S., Ahmad T., Borg E., Falzon M., Khiroya R., Marafioti T., Sharp A., Pilotti C., Dhanda H. K., Chan K., Gower N., Leslie R., Smith S., Nicholson A. G., Lim E., Herrero J., Castignani C., Larose Cadieux E., Demeulemeester J., Van Loo P., Peggs K. S., Veiga C., Royle G., Collins-Fekete C. -A., Procter A. J., Nair A., Ahmed A., Taylor M. N., Navani N., Thakrar R. M., Lawrence D., Patrini D., Nye E., Stone R. K., Chuter D., MacKenzie M., Fraioli F., Ashford P., Janes S. M., Tanic M., Beck S., Rice A., Devaraj A., Proli C., Kaniu D., Bhayani H., Chavan H., Raubenheimer H., Ambrose L., Malima M., Fernandes N., De Sousa P., Shah P., Booth S., Buderi S. I., Jordan S., Begum S., Boleti E., Stewart A., Magness A., Weeden C. E., Levi D., Gronroos E., Goldman J., Escudero M., Hobson P., Vendramin R., Boeing S., Denner T., Barbe V., Lu W. -T., Hill W., Naito Y., Ramsden Z., Grapa A., Zhang H., AbdulJabbar K., Pan X., Gilbert K., Karamani A., Chain B., Pearce D. R., Karagianni D., Hoxha E., Galvez-Cancino F., Stavrou G., Mastrokalos G., Lowe H. L., Matos I., Reading J. L., Hartley J. A., Selvaraju K., Chen K., Ensell L., Shah M., Vasquez M., Litovchenko M., Chervova O., Pawlik P., Hynds R. E., Lopez S., Gamble S., Ung S. K. A., Bola S. K., Mourikis T. P., Spanswick V., Wu Y., Martinoni Hoogenboom E., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Stephens R. C. M., Bandula S., Wong Y. N. S., Clark T., Cheyne H., Khalil M., Richardson S., Cruickshank T., Naidu B., Matharu G., Shaw J. A., Riley J., Primrose L., Le Quesne J., Blyth K. G., Kerr A., Clipson A., Chaturvedi A., Dive C., Rothwell D. G., Kilgour E., Tugwood J., Priest L., Oliveira P., Crosbie P., Price G., Cave J., Kerr K. M., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Kirk A., Thomas M., Asif M., Kostoulas N., Bilancia R., Middleton G., Shackcloth M. J., Leek A., Hodgkinson J. D., Totten N., Dick C., Robinson L., Russell P., Hewish M., Danson S., Lester J. F., Gomes F., Brown K., Carter M., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Alzetani A., Richards J., Scarlett L., Ingram P., Chee S., Austin S., Bajaj A., Nakas A., Sodha-Ramdeen A., Fennell D. A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Aerts H. J. W. L., Kaufmann T. L., Schwarz R. F., Kisistok J., Sokac M., Diossy M., Szallasi Z., Dijkstra K., Yuan Y., Byrne F., Boos L. A., Shum B., Gerard C. L., Schmitt A. M., Messiou C., Cunningham D., Chau I., Starling N., Turner N., Welsh L., Jones R. L., Droney J., Banerjee S., Tatham K. C., Jhanji S., Harrington K., Okines A., Reid A., Young K., Furness A. J. S., Pickering L., Nicholson E., Kumar S., Wilkinson K. A., Swerdlow A., Wilkinson R. J., Hiley C. T., Litchfield K., McGranahan N., Jamal-Hanjani M., Larkin J., Lee S. -H., Turajlic S., Swanton C., Downward J., Kassiotis G., Ng, K, Boumelha, J, Enfield, K, Almagro, J, Cha, H, Pich, O, Karasaki, T, Moore, D, Salgado, R, Sivakumar, M, Young, G, Molina-Arcas, M, de Carne Trecesson, S, Anastasiou, P, Fendler, A, Au, L, Shepherd, S, Martinez-Ruiz, C, Puttick, C, Black, J, Watkins, T, Kim, H, Shim, S, Faulkner, N, Attig, J, Veeriah, S, Magno, N, Ward, S, Frankell, A, Al Bakir, M, Lim, E, Hill, M, Wilson, G, Cook, D, Birkbak, N, Behrens, A, Yousaf, N, Popat, S, Hackshaw, A, Rowan, A, Huebner, A, Campbell, B, Bailey, C, Lee, C, Biswas, D, Colliver, E, Athanasopoulou, F, Zhai, H, Rane, J, Grigoriadis, K, Dietzen, M, Leung, M, Angelova, M, Lucas, O, Al-Sawaf, O, Rosenthal, R, Nicod, J, Bunkum, A, Toncheva, A, Abbosh, C, Richard, C, Naceur-Lombardelli, C, Gimeno-Valiente, F, Lam, J, Thol, K, Thakkar, K, Werner Sunderland, M, Forster, M, Kanu, N, Prymas, P, Bentham, R, Saghafinia, S, Quezada, S, Vanloo, S, Zaccaria, S, Lee, S, Hessey, S, Liu, W, Papadatos-Pastos, D, Wilson, J, Benafif, S, Ahmad, T, Borg, E, Falzon, M, Khiroya, R, Marafioti, T, Sharp, A, Pilotti, C, Dhanda, H, Chan, K, Gower, N, Leslie, R, Smith, S, Nicholson, A, Herrero, J, Castignani, C, Larose Cadieux, E, Demeulemeester, J, Van Loo, P, Peggs, K, Veiga, C, Royle, G, Collins-Fekete, C, Procter, A, Nair, A, Ahmed, A, Taylor, M, Navani, N, Thakrar, R, Lawrence, D, Patrini, D, Nye, E, Stone, R, Chuter, D, Mackenzie, M, Fraioli, F, Ashford, P, Janes, S, Tanic, M, Beck, S, Rice, A, Devaraj, A, Proli, C, Kaniu, D, Bhayani, H, Chavan, H, Raubenheimer, H, Ambrose, L, Malima, M, Fernandes, N, De Sousa, P, Shah, P, Booth, S, Buderi, S, Jordan, S, Begum, S, Boleti, E, Stewart, A, Magness, A, Weeden, C, Levi, D, Gronroos, E, Goldman, J, Escudero, M, Hobson, P, Vendramin, R, Boeing, S, Denner, T, Barbe, V, Lu, W, Hill, W, Naito, Y, Ramsden, Z, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Gilbert, K, Karamani, A, Chain, B, Pearce, D, Karagianni, D, Hoxha, E, Galvez-Cancino, F, Stavrou, G, Mastrokalos, G, Lowe, H, Matos, I, Reading, J, Hartley, J, Selvaraju, K, Chen, K, Ensell, L, Shah, M, Vasquez, M, Litovchenko, M, Chervova, O, Pawlik, P, Hynds, R, Lopez, S, Gamble, S, Ung, S, Bola, S, Mourikis, T, Spanswick, V, Wu, Y, Martinoni Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Stephens, R, Bandula, S, Wong, Y, Clark, T, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Naidu, B, Matharu, G, Shaw, J, Riley, J, Primrose, L, Le Quesne, J, Blyth, K, Kerr, A, Clipson, A, Chaturvedi, A, Dive, C, Rothwell, D, Kilgour, E, Tugwood, J, Priest, L, Oliveira, P, Crosbie, P, Price, G, Cave, J, Kerr, K, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Kirk, A, Thomas, M, Asif, M, Kostoulas, N, Bilancia, R, Middleton, G, Shackcloth, M, Leek, A, Hodgkinson, J, Totten, N, Dick, C, Robinson, L, Russell, P, Hewish, M, Danson, S, Lester, J, Gomes, F, Brown, K, Carter, M, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Alzetani, A, Richards, J, Scarlett, L, Ingram, P, Chee, S, Austin, S, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Fennell, D, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Aerts, H, Kaufmann, T, Schwarz, R, Kisistok, J, Sokac, M, Diossy, M, Szallasi, Z, Dijkstra, K, Yuan, Y, Byrne, F, Boos, L, Shum, B, Gerard, C, Schmitt, A, Messiou, C, Cunningham, D, Chau, I, Starling, N, Turner, N, Welsh, L, Jones, R, Droney, J, Banerjee, S, Tatham, K, Jhanji, S, Harrington, K, Okines, A, Reid, A, Young, K, Furness, A, Pickering, L, Nicholson, E, Kumar, S, Wilkinson, K, Swerdlow, A, Wilkinson, R, Hiley, C, Litchfield, K, Mcgranahan, N, Jamal-Hanjani, M, Larkin, J, Turajlic, S, Swanton, C, Downward, J, Kassiotis, G, Ng K. W., Boumelha J., Enfield K. S. S., Almagro J., Cha H., Pich O., Karasaki T., Moore D. A., Salgado R., Sivakumar M., Young G., Molina-Arcas M., de Carne Trecesson S., Anastasiou P., Fendler A., Au L., Shepherd S. T. C., Martinez-Ruiz C., Puttick C., Black J. R. M., Watkins T. B. K., Kim H., Shim S., Faulkner N., Attig J., Veeriah S., Magno N., Ward S., Frankell A. M., Al Bakir M., Lim E. L., Hill M. S., Wilson G. A., Cook D. E., Birkbak N. J., Behrens A., Yousaf N., Popat S., Hackshaw A., Rowan A., Huebner A., Campbell B. B., Bailey C., Lee C., Biswas D., Colliver E., Athanasopoulou F., Zhai H., Rane J. K., Grigoriadis K., Dietzen M., Leung M., Angelova M., Lucas O., Al-Sawaf O., Rosenthal R., Nicod J., Bunkum A., Toncheva A., Abbosh C., Richard C., Naceur-Lombardelli C., Gimeno-Valiente F., Lam J. M., Thol K., Thakkar K., Werner Sunderland M., Forster M. D., Kanu N., Prymas P., Bentham R., Saghafinia S., Quezada S. A., Vanloo S., Zaccaria S., Lee S. M., Hessey S., Liu W. K., Papadatos-Pastos D., Wilson J., Benafif S., Ahmad T., Borg E., Falzon M., Khiroya R., Marafioti T., Sharp A., Pilotti C., Dhanda H. K., Chan K., Gower N., Leslie R., Smith S., Nicholson A. G., Lim E., Herrero J., Castignani C., Larose Cadieux E., Demeulemeester J., Van Loo P., Peggs K. S., Veiga C., Royle G., Collins-Fekete C. -A., Procter A. J., Nair A., Ahmed A., Taylor M. N., Navani N., Thakrar R. M., Lawrence D., Patrini D., Nye E., Stone R. K., Chuter D., MacKenzie M., Fraioli F., Ashford P., Janes S. M., Tanic M., Beck S., Rice A., Devaraj A., Proli C., Kaniu D., Bhayani H., Chavan H., Raubenheimer H., Ambrose L., Malima M., Fernandes N., De Sousa P., Shah P., Booth S., Buderi S. I., Jordan S., Begum S., Boleti E., Stewart A., Magness A., Weeden C. E., Levi D., Gronroos E., Goldman J., Escudero M., Hobson P., Vendramin R., Boeing S., Denner T., Barbe V., Lu W. -T., Hill W., Naito Y., Ramsden Z., Grapa A., Zhang H., AbdulJabbar K., Pan X., Gilbert K., Karamani A., Chain B., Pearce D. R., Karagianni D., Hoxha E., Galvez-Cancino F., Stavrou G., Mastrokalos G., Lowe H. L., Matos I., Reading J. L., Hartley J. A., Selvaraju K., Chen K., Ensell L., Shah M., Vasquez M., Litovchenko M., Chervova O., Pawlik P., Hynds R. E., Lopez S., Gamble S., Ung S. K. A., Bola S. K., Mourikis T. P., Spanswick V., Wu Y., Martinoni Hoogenboom E., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Stephens R. C. M., Bandula S., Wong Y. N. S., Clark T., Cheyne H., Khalil M., Richardson S., Cruickshank T., Naidu B., Matharu G., Shaw J. A., Riley J., Primrose L., Le Quesne J., Blyth K. G., Kerr A., Clipson A., Chaturvedi A., Dive C., Rothwell D. G., Kilgour E., Tugwood J., Priest L., Oliveira P., Crosbie P., Price G., Cave J., Kerr K. M., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Kirk A., Thomas M., Asif M., Kostoulas N., Bilancia R., Middleton G., Shackcloth M. J., Leek A., Hodgkinson J. D., Totten N., Dick C., Robinson L., Russell P., Hewish M., Danson S., Lester J. F., Gomes F., Brown K., Carter M., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Alzetani A., Richards J., Scarlett L., Ingram P., Chee S., Austin S., Bajaj A., Nakas A., Sodha-Ramdeen A., Fennell D. A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Aerts H. J. W. L., Kaufmann T. L., Schwarz R. F., Kisistok J., Sokac M., Diossy M., Szallasi Z., Dijkstra K., Yuan Y., Byrne F., Boos L. A., Shum B., Gerard C. L., Schmitt A. M., Messiou C., Cunningham D., Chau I., Starling N., Turner N., Welsh L., Jones R. L., Droney J., Banerjee S., Tatham K. C., Jhanji S., Harrington K., Okines A., Reid A., Young K., Furness A. J. S., Pickering L., Nicholson E., Kumar S., Wilkinson K. A., Swerdlow A., Wilkinson R. J., Hiley C. T., Litchfield K., McGranahan N., Jamal-Hanjani M., Larkin J., Lee S. -H., Turajlic S., Swanton C., Downward J., and Kassiotis G.
Abstract: B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS)1,2. Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive1,2. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma3. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response.
Published: 2023

8. The evolution of lung cancer and impact of subclonal selection in TRACERx

Author: Frankell, A, Dietzen, M, Al Bakir, M, Lim, E, Karasaki, T, Ward, S, Veeriah, S, Colliver, E, Huebner, A, Bunkum, A, Hill, M, Grigoriadis, K, Moore, D, Black, J, Liu, W, Thol, K, Pich, O, Watkins, T, Naceur-Lombardelli, C, Cook, D, Salgado, R, Wilson, G, Bailey, C, Angelova, M, Bentham, R, Martinez-Ruiz, C, Abbosh, C, Nicholson, A, Le Quesne, J, Biswas, D, Rosenthal, R, Puttick, C, Hessey, S, Lee, C, Prymas, P, Toncheva, A, Smith, J, Xing, W, Nicod, J, Price, G, Kerr, K, Naidu, B, Middleton, G, Blyth, K, Fennell, D, Forster, M, Lee, S, Falzon, M, Hewish, M, Shackcloth, M, Benafif, S, Russell, P, Boleti, E, Krebs, M, Lester, J, Papadatos-Pastos, D, Ahmad, T, Thakrar, R, Lawrence, D, Navani, N, Janes, S, Dive, C, Blackhall, F, Summers, Y, Cave, J, Marafioti, T, Herrero, J, Quezada, S, Peggs, K, Schwarz, R, Van Loo, P, Miedema, D, Birkbak, N, Hiley, C, Hackshaw, A, Zaccaria, S, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Matharu, G, Shaw, J, Riley, J, Primrose, L, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Gilbert, K, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Gomes, F, Brown, K, Carter, M, Chaturvedi, A, Priest, L, Oliveira, P, Lindsay, C, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Kilgour, E, Aerts, H, Kaufmann, T, Szallasi, Z, Kisistok, J, Sokac, M, Diossy, M, Demeulemeester, J, Stewart, A, Magness, A, Rowan, A, Karamani, A, Chain, B, Campbell, B, Castignani, C, Weeden, C, Richard, C, Pearce, D, Karagianni, D, Levi, D, Hoxha, E, Larose Cadieux, E, Nye, E, Gronroos, E, Galvez-Cancino, F, Athanasopoulou, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Zhai, H, Lowe, H, Matos, I, Goldman, J, Reading, J, Rane, J, Lam, J, Hartley, J, Enfield, K, Selvaraju, K, Litchfield, K, Ng, K, Chen, K, Dijkstra, K, Thakkar, K, Ensell, L, Shah, M, Vasquez, M, Litovchenko, M, Werner Sunderland, M, Leung, M, Escudero, M, Tanic, M, Sivakumar, M, Kanu, N, Chervova, O, Lucas, O, Al-Sawaf, O, Hobson, P, Pawlik, P, Stone, R, Hynds, R, Vendramin, R, Saghafinia, S, Lopez, S, Gamble, S, Ung, S, Vanloo, S, Boeing, S, Beck, S, Bola, S, Denner, T, Mourikis, T, Spanswick, V, Barbe, V, Lu, W, Hill, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Clark, T, Borg, E, Wilson, J, Procter, A, Ahmed, A, Taylor, M, Nair, A, Patrini, D, Martinoni Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Bandula, S, Sharp, A, Smith, S, Gower, N, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Scarlett, L, Richards, J, Ingram, P, Austin, S, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Fernandes, N, Shah, P, Proli, C, Danson, S, Robinson, L, Dick, C, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Jamal-Hanjani, M, Mcgranahan, N, Swanton, C, Frankell A. M., Dietzen M., Al Bakir M., Lim E. L., Karasaki T., Ward S., Veeriah S., Colliver E., Huebner A., Bunkum A., Hill M. S., Grigoriadis K., Moore D. A., Black J. R. M., Liu W. K., Thol K., Pich O., Watkins T. B. K., Naceur-Lombardelli C., Cook D. E., Salgado R., Wilson G. A., Bailey C., Angelova M., Bentham R., Martinez-Ruiz C., Abbosh C., Nicholson A. G., Le Quesne J., Biswas D., Rosenthal R., Puttick C., Hessey S., Lee C., Prymas P., Toncheva A., Smith J., Xing W., Nicod J., Price G., Kerr K. M., Naidu B., Middleton G., Blyth K. G., Fennell D. A., Forster M. D., Lee S. M., Falzon M., Hewish M., Shackcloth M. J., Lim E., Benafif S., Russell P., Boleti E., Krebs M. G., Lester J. F., Papadatos-Pastos D., Ahmad T., Thakrar R. M., Lawrence D., Navani N., Janes S. M., Dive C., Blackhall F. H., Summers Y., Cave J., Marafioti T., Herrero J., Quezada S. A., Peggs K. S., Schwarz R. F., Van Loo P., Miedema D. M., Birkbak N. J., Hiley C. T., Hackshaw A., Zaccaria S., Bajaj A., Nakas A., Sodha-Ramdeen A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Matharu G., Shaw J. A., Riley J., Primrose L., Cheyne H., Khalil M., Richardson S., Cruickshank T., Gilbert K., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Gomes F., Brown K., Carter M., Chaturvedi A., Priest L., Oliveira P., Lindsay C. R., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Kilgour E., Aerts H. J. W. L., Kaufmann T. L., Szallasi Z., Kisistok J., Sokac M., Diossy M., Demeulemeester J., Stewart A., Magness A., Rowan A., Karamani A., Chain B., Campbell B. B., Castignani C., Weeden C. E., Richard C., Pearce D. R., Karagianni D., Levi D., Hoxha E., Larose Cadieux E., Nye E., Gronroos E., Galvez-Cancino F., Athanasopoulou F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G., Zhai H., Lowe H. L., Matos I., Goldman J., Reading J. L., Rane J. K., Lam J. M., Hartley J. A., Enfield K. S. S., Selvaraju K., Litchfield K., Ng K. W., Chen K., Dijkstra K., Thakkar K., Ensell L., Shah M., Vasquez M., Litovchenko M., Werner Sunderland M., Leung M., Escudero M., Tanic M., Sivakumar M., Kanu N., Chervova O., Lucas O., Al-Sawaf O., Hobson P., Pawlik P., Stone R. K., Hynds R. E., Vendramin R., Saghafinia S., Lopez S., Gamble S., Ung S. K. A., Vanloo S., Boeing S., Beck S., Bola S. K., Denner T., Mourikis T. P., Spanswick V., Barbe V., Lu W. -T., Hill W., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Clark T., Borg E., Wilson J., Procter A. J., Ahmed A., Taylor M. N., Nair A., Patrini D., Martinoni Hoogenboom E., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Khiroya R., Stephens R. C., Wong Y. N. S., Bandula S., Sharp A., Smith S., Gower N., Dhanda H. K., Chan K., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Scarlett L., Richards J., Ingram P., Austin S., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Fernandes N., Shah P., Proli C., Danson S., Robinson L., Dick C., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Jamal-Hanjani M., McGranahan N., Swanton C., Frankell, A, Dietzen, M, Al Bakir, M, Lim, E, Karasaki, T, Ward, S, Veeriah, S, Colliver, E, Huebner, A, Bunkum, A, Hill, M, Grigoriadis, K, Moore, D, Black, J, Liu, W, Thol, K, Pich, O, Watkins, T, Naceur-Lombardelli, C, Cook, D, Salgado, R, Wilson, G, Bailey, C, Angelova, M, Bentham, R, Martinez-Ruiz, C, Abbosh, C, Nicholson, A, Le Quesne, J, Biswas, D, Rosenthal, R, Puttick, C, Hessey, S, Lee, C, Prymas, P, Toncheva, A, Smith, J, Xing, W, Nicod, J, Price, G, Kerr, K, Naidu, B, Middleton, G, Blyth, K, Fennell, D, Forster, M, Lee, S, Falzon, M, Hewish, M, Shackcloth, M, Benafif, S, Russell, P, Boleti, E, Krebs, M, Lester, J, Papadatos-Pastos, D, Ahmad, T, Thakrar, R, Lawrence, D, Navani, N, Janes, S, Dive, C, Blackhall, F, Summers, Y, Cave, J, Marafioti, T, Herrero, J, Quezada, S, Peggs, K, Schwarz, R, Van Loo, P, Miedema, D, Birkbak, N, Hiley, C, Hackshaw, A, Zaccaria, S, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Matharu, G, Shaw, J, Riley, J, Primrose, L, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Gilbert, K, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Gomes, F, Brown, K, Carter, M, Chaturvedi, A, Priest, L, Oliveira, P, Lindsay, C, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Kilgour, E, Aerts, H, Kaufmann, T, Szallasi, Z, Kisistok, J, Sokac, M, Diossy, M, Demeulemeester, J, Stewart, A, Magness, A, Rowan, A, Karamani, A, Chain, B, Campbell, B, Castignani, C, Weeden, C, Richard, C, Pearce, D, Karagianni, D, Levi, D, Hoxha, E, Larose Cadieux, E, Nye, E, Gronroos, E, Galvez-Cancino, F, Athanasopoulou, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Zhai, H, Lowe, H, Matos, I, Goldman, J, Reading, J, Rane, J, Lam, J, Hartley, J, Enfield, K, Selvaraju, K, Litchfield, K, Ng, K, Chen, K, Dijkstra, K, Thakkar, K, Ensell, L, Shah, M, Vasquez, M, Litovchenko, M, Werner Sunderland, M, Leung, M, Escudero, M, Tanic, M, Sivakumar, M, Kanu, N, Chervova, O, Lucas, O, Al-Sawaf, O, Hobson, P, Pawlik, P, Stone, R, Hynds, R, Vendramin, R, Saghafinia, S, Lopez, S, Gamble, S, Ung, S, Vanloo, S, Boeing, S, Beck, S, Bola, S, Denner, T, Mourikis, T, Spanswick, V, Barbe, V, Lu, W, Hill, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Clark, T, Borg, E, Wilson, J, Procter, A, Ahmed, A, Taylor, M, Nair, A, Patrini, D, Martinoni Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Bandula, S, Sharp, A, Smith, S, Gower, N, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Scarlett, L, Richards, J, Ingram, P, Austin, S, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Fernandes, N, Shah, P, Proli, C, Danson, S, Robinson, L, Dick, C, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Jamal-Hanjani, M, Mcgranahan, N, Swanton, C, Frankell A. M., Dietzen M., Al Bakir M., Lim E. L., Karasaki T., Ward S., Veeriah S., Colliver E., Huebner A., Bunkum A., Hill M. S., Grigoriadis K., Moore D. A., Black J. R. M., Liu W. K., Thol K., Pich O., Watkins T. B. K., Naceur-Lombardelli C., Cook D. E., Salgado R., Wilson G. A., Bailey C., Angelova M., Bentham R., Martinez-Ruiz C., Abbosh C., Nicholson A. G., Le Quesne J., Biswas D., Rosenthal R., Puttick C., Hessey S., Lee C., Prymas P., Toncheva A., Smith J., Xing W., Nicod J., Price G., Kerr K. M., Naidu B., Middleton G., Blyth K. G., Fennell D. A., Forster M. D., Lee S. M., Falzon M., Hewish M., Shackcloth M. J., Lim E., Benafif S., Russell P., Boleti E., Krebs M. G., Lester J. F., Papadatos-Pastos D., Ahmad T., Thakrar R. M., Lawrence D., Navani N., Janes S. M., Dive C., Blackhall F. H., Summers Y., Cave J., Marafioti T., Herrero J., Quezada S. A., Peggs K. S., Schwarz R. F., Van Loo P., Miedema D. M., Birkbak N. J., Hiley C. T., Hackshaw A., Zaccaria S., Bajaj A., Nakas A., Sodha-Ramdeen A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Matharu G., Shaw J. A., Riley J., Primrose L., Cheyne H., Khalil M., Richardson S., Cruickshank T., Gilbert K., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Gomes F., Brown K., Carter M., Chaturvedi A., Priest L., Oliveira P., Lindsay C. R., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Kilgour E., Aerts H. J. W. L., Kaufmann T. L., Szallasi Z., Kisistok J., Sokac M., Diossy M., Demeulemeester J., Stewart A., Magness A., Rowan A., Karamani A., Chain B., Campbell B. B., Castignani C., Weeden C. E., Richard C., Pearce D. R., Karagianni D., Levi D., Hoxha E., Larose Cadieux E., Nye E., Gronroos E., Galvez-Cancino F., Athanasopoulou F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G., Zhai H., Lowe H. L., Matos I., Goldman J., Reading J. L., Rane J. K., Lam J. M., Hartley J. A., Enfield K. S. S., Selvaraju K., Litchfield K., Ng K. W., Chen K., Dijkstra K., Thakkar K., Ensell L., Shah M., Vasquez M., Litovchenko M., Werner Sunderland M., Leung M., Escudero M., Tanic M., Sivakumar M., Kanu N., Chervova O., Lucas O., Al-Sawaf O., Hobson P., Pawlik P., Stone R. K., Hynds R. E., Vendramin R., Saghafinia S., Lopez S., Gamble S., Ung S. K. A., Vanloo S., Boeing S., Beck S., Bola S. K., Denner T., Mourikis T. P., Spanswick V., Barbe V., Lu W. -T., Hill W., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Clark T., Borg E., Wilson J., Procter A. J., Ahmed A., Taylor M. N., Nair A., Patrini D., Martinoni Hoogenboom E., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Khiroya R., Stephens R. C., Wong Y. N. S., Bandula S., Sharp A., Smith S., Gower N., Dhanda H. K., Chan K., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Scarlett L., Richards J., Ingram P., Austin S., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Fernandes N., Shah P., Proli C., Danson S., Robinson L., Dick C., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Jamal-Hanjani M., McGranahan N., and Swanton C.
Abstract: Lung cancer is the leading cause of cancer-associated mortality worldwide1. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFR mutations and for RET, ROS1, ALK and MET oncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1 year after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource.
Published: 2023

9. 93P Circulating cell-free DNA fragmentation profiles during systemic therapy of advanced-stage non-small cell lung cancer patients

Author: Milovanovic, J., primary, Boljevic, I., additional, Spasic, J., additional, Topalovic, M., additional, Krivokuca, A., additional, Cavic, M., additional, and Tanic, M., additional
Published: 2023
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10. 953P EGFR mutation testing from pleural effusions of advanced lung adenocarcinoma patients in Serbia

Author: Cavic, M., primary, Damjanovic, A., additional, Boljevic, I., additional, Pavlovic, M., additional, Stefanovic, A., additional, Zivic, K., additional, Vukovic, M., additional, Tanic, M., additional, and Jankovic, R., additional
Published: 2022
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11. 28P Identification of convergent gene repression mechanisms through integrative genomic and DNA methylation analysis in NSCLC

Author: Castignani, C., primary, Gimeno-Valiente, F., additional, Larose Cadieux, E., additional, Chen, K., additional, Mensah, N., additional, Chervova, O., additional, Watkins, T., additional, Dhami, P., additional, Vaikkinen, H., additional, Saghafinia, S., additional, Karasaki, T., additional, Hiley, C., additional, Feber, A., additional, TRACERx, C., additional, Demeulemeester, J., additional, Tanic, M., additional, Beck, S., additional, van Loo, P., additional, Swanton, C., additional, and Kanu, N., additional
Published: 2022
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12. Two Decades of Progress in Personalized Medicine of Colorectal Cancer in Serbia-Insights from the Institute for Oncology and Radiology of Serbia.

Author: Cavic M, Nikolic N, Marinkovic M, Damjanovic A, Krivokuca A, Tanic M, Radulovic M, Stanojevic A, Pejnovic L, Djordjic Crnogorac M, Djuric A, Vukovic M, Stevanovic V, Kijac J, Karadzic V, Nikolic S, Stojanovic-Rundic S, Jankovic R, and Spasic J
Abstract: Background: It is projected that, by 2040, the number of new cases of colorectal cancer (CRC) will increase to 3.2 million, and the number of deaths to 1.6 million, highlighting the need for prevention strategies, early detection and adequate follow-up. In this study, we aimed to provide an overview of the progress in personalized medicine of CRC in Serbia, with results and insights from the Institute for Oncology and Radiology of Serbia (IORS), and to propose guidance for tackling observed challenges in the future., Methods: Epidemiological data were derived from official global and national cancer registries and IORS electronic medical records. Germline genetic testing for Lynch syndrome was performed by Next Generation Sequencing. RAS and BRAF mutation analyses were performed using qPCR diagnostic kits., Results: Epidemiology and risk factors, prevention and early detection programs, as well as treatment options and scientific advances have been described in detail. Out of 103 patients who underwent germline testing for Lynch syndrome, 19 (18.4%) showed a mutation in MMR genes with pathogenic or likely pathogenic significance and 8 (7.8%) in other CRC-associated genes ( APC , CHEK2 , MUTYH ). Of 6369 tested patients, 50.43% had a mutation in KRAS or NRAS genes, while 9.54% had the V600 mutation in the BRAF gene., Conclusions: Although significant improvements in CRC management have occurred globally in recent years, a strategic approach leading to population-based systemic solutions is required. The high incidence of young-onset CRC and the growing elderly population due to a rise in life expectancy will be especially important factors for countries with limited healthcare resources like Serbia.
Published: 2024
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13. Global Practice Patterns in the Evaluation of Non-Obstructive Azoospermia: Results of a World-Wide Survey and Expert Recommendations.

Author: Shah R, Rambhatla A, Atmoko W, Martinez M, Ziouziou I, Kothari P, Tadros N, Phuoc NHV, Kavoussi P, Harraz A, Salvio G, Gul M, Hamoda T, Toprak T, Birowo P, Ko E, Arafa M, Ghayda RA, Karthikeyan VS, Saleh R, Russo GI, Pinggera GM, Chung E, Savira M, Colpi GM, Zohdy W, Pescatori E, Park HJ, Fukuhara S, Tsujimura A, Rojas-Cruz C, Marino A, Mak SK, Amar E, Ibrahim W, Sindhwani P, Alhathal N, Busetto GM, Al Hashimi M, El-Sakka A, Ramazan A, Dimitriadis F, Timpano M, Jezek D, Altay B, Zylbersztejn DS, Wong MY, Moon DG, Wyns C, Gamidov S, Akhavizadegan H, Franceschelli A, Aydos K, Quang VN, Ashour S, Al Dayel A, Al-Marhoon MS, Micic S, Binsaleh S, Hussein A, Elbardisi H, Mostafa T, Taha E, Ramsay J, Zachariou A, Abdelrahman IFS, Rajmil O, Kalkanli A, Molina JMC, Bocu K, Duarsa GWK, Ceker G, Serefoglu EC, Bahar F, Gherabi N, Kuroda S, Bouzouita A, Gudeloglu A, Ceyhan E, Hasan MSM, Musa MU, Motawi A, Chak-Lam C, Taniguchi H, Ho CCK, Vazquez JFS, Mutambirwa S, Gungor ND, Bendayan M, Giulioni C, Baser A, Falcone M, Boeri L, Blecher G, Kheradmand A, Sethupathy T, Adriansjah R, Narimani N, Konstantinidis C, Nguyen TT, Japari A, Dolati P, Singh K, Ozer C, Sarikaya S, Sheibak N, Bosco NJ, Özkent MS, Le ST, Sokolakis I, Katz D, Smith R, Truong MN, Le TV, Huang Z, Deger MD, Arslan U, Calik G, Franco G, Rashed A, Kahraman O, Andreadakis S, Putra R, Balercia G, Khalafalla K, Cannarella R, Tuấn AĐ, El Meliegy A, Zilaitiene B, Ramirez MLZ, Giacone F, Calogero AE, Makarounis K, Jindal S, Hoai BN, Banthia R, Peña MR, Moorthy D, Adamyan A, Kulaksiz D, Kandil H, Sofikitis N, Salzano C, Jungwirth A, Banka SR, Mierzwa TC, Turunç T, Jain D, Avoyan A, Salacone P, Kadıoğlu A, Gupta C, Lin H, Shamohammadi I, Mogharabian N, Barrett T, Danacıoğlu YO, Crafa A, Daoud S, Malhotra V, Almardawi A, Selim OM, Moussa M, Haghdani S, Duran MB, Kunz Y, Preto M, Eugeni E, Nguyen T, Elshahid AR, Suyono SS, Parikesit D, Nada E, Orozco EG, Boitrelle F, Trang NTM, Jamali M, Nair R, Ruzaev M, Gadda F, Thomas C, Ferreira RH, Gul U, Maruccia S, Kanbur A, Kinzikeeva E, Abumelha S, Quang N, Kosgi R, Gokalp F, Soebadi MA, Paul GM, Sajadi H, Gupte D, Ambar RF, Sogutdelen E, Singla K, Basurkano A, Kim SHK, Gilani MAS, Nagao K, Brodjonegoro SR, Rezano A, Elkhouly M, Mazzilli R, Farsi HMA, Ba HN, Alali H, Kafetzis D, Long TQT, Alsaid S, Cuong HBN, Oleksandr K, Mustafa A, Acosta H, Pai H, Şahin B, Arianto E, Teo C, Jayaprakash SP, Rachman RI, Yenice MG, Sefrioui O, Paghdar S, Priyadarshi S, Tanic M, Alfatlawy NK, Rizaldi F, Vishwakarma RB, Kanakis G, Cherian DT, Lee J, Galstyan R, Keskin H, Wurzacher J, Seno DH, Noegroho BS, Margiana R, Javed Q, Castiglioni F, Tanwar R, Puigvert A, Kaya C, Purnomo M, Yazbeck C, Amir A, Borges E, Bellavia M, Deswanto IA, V VK, Liguori G, Minh DH, Siddiqi K, Colombo F, Zini A, Patel N, Çayan S, Al-Kawaz U, Ragab M, Hebrard GH, Hoffmann I, Efesoy O, Saylam B, and Agarwal A
Abstract: Purpose: Non-obstructive azoospermia (NOA) represents the persistent absence of sperm in ejaculate without obstruction, stemming from diverse disease processes. This survey explores global practices in NOA diagnosis, comparing them with guidelines and offering expert recommendations., Materials and Methods: A 56-item questionnaire survey on NOA diagnosis and management was conducted globally from July to September 2022. This paper focuses on part 1, evaluating NOA diagnosis. Data from 367 participants across 49 countries were analyzed descriptively, with a Delphi process used for expert recommendations., Results: Of 336 eligible responses, most participants were experienced attending physicians (70.93%). To diagnose azoospermia definitively, 81.7% requested two semen samples. Commonly ordered hormone tests included serum follicle-stimulating hormone (FSH) (97.0%), total testosterone (92.9%), and luteinizing hormone (86.9%). Genetic testing was requested by 66.6%, with karyotype analysis (86.2%) and Y chromosome microdeletions (88.3%) prevalent. Diagnostic testicular biopsy, distinguishing obstructive azoospermia (OA) from NOA, was not performed by 45.1%, while 34.6% did it selectively. Differentiation relied on physical examination (76.1%), serum hormone profiles (69.6%), and semen tests (68.1%). Expectations of finding sperm surgically were higher in men with normal FSH, larger testes, and a history of sperm in ejaculate., Conclusions: This expert survey, encompassing 367 participants from 49 countries, unveils congruence with recommended guidelines in NOA diagnosis. However, noteworthy disparities in practices suggest a need for evidence-based, international consensus guidelines to standardize NOA evaluation, addressing existing gaps in professional recommendations., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)
Published: 2024
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14. Global Practice Patterns and Variations in the Medical and Surgical Management of Non-Obstructive Azoospermia: Results of a World-Wide Survey, Guidelines and Expert Recommendations.

Author: Rambhatla A, Shah R, Ziouziou I, Kothari P, Salvio G, Gul M, Hamoda T, Kavoussi P, Atmoko W, Toprak T, Birowo P, Ko E, Arafa M, Ghayda RA, Karthikeyan VS, Russo GI, Pinggera GM, Chung E, Harraz AM, Martinez M, Phuoc NHV, Tadros N, Saleh R, Savira M, Colpi GM, Zohdy W, Pescatori E, Park HJ, Fukuhara S, Tsujimura A, Rojas-Cruz C, Marino A, Mak SK, Amar E, Ibrahim W, Sindhwani P, Alhathal N, Busetto GM, Al Hashimi M, El-Sakka A, Ramazan A, Dimitriadis F, Timpano M, Jezek D, Altay B, Zylbersztejn DS, Wong MY, Moon DG, Wyns C, Gamidov S, Akhavizadegan H, Franceschelli A, Aydos K, Quang N, Ashour S, Al Dayel A, Al-Marhoon MS, Micic S, Binsaleh S, Hussein A, Elbardisi H, Mostafa T, Ramsay J, Zachariou A, Abdelrahman IFS, Rajmil O, Kalkanli A, Molina JMC, Bocu K, Duarsa GWK, Çeker G, Serefoglu EC, Bahar F, Gherabi N, Kuroda S, Bouzouita A, Gudeloglu A, Ceyhan E, Hasan MSM, Musa MU, Motawi A, Cho CL, Taniguchi H, Ho CCK, Vazquez JFS, Mutambirwa S, Gungor ND, Bendayan M, Giulioni C, Baser A, Falcone M, Boeri L, Blecher G, Kheradmand A, Sethupathy T, Adriansjah R, Narimani N, Konstantinidis C, Nguyen TT, Japari A, Dolati P, Singh K, Ozer C, Sarikaya S, Sheibak N, Bosco NJ, Özkent MS, Le ST, Sokolakis I, Katz D, Smith R, Truong MN, Le TV, Huang Z, Deger MD, Arslan U, Calik G, Franco G, Rashed A, Kahraman O, Andreadakis S, Putra R, Balercia G, Khalafalla K, Cannarella R, Tuân AÐ, El Meliegy A, Zilaitiene B, Ramirez MLZ, Giacone F, Calogero AE, Makarounis K, Jindal S, Hoai BN, Banthia R, Peña MR, Moorthy D, Adamyan A, Kulaksiz D, Kandil H, Sofikitis N, Salzano C, Jungwirth A, Banka SR, Mierzwa TC, Turunç T, Jain D, Avoyan A, Salacone P, Kadıoğlu A, Gupta C, Lin H, Shamohammadi I, Mogharabian N, Barrett T, Danacıoğlu YO, Crafa A, Daoud S, Malhotra V, Almardawi A, Selim OM, Moussa M, Haghdani S, Duran MB, Kunz Y, Preto M, Eugeni E, Nguyen T, Elshahid AR, Suyono SS, Parikesit D, Nada E, Orozco EG, Boitrelle F, Trang NTM, Jamali M, Nair R, Ruzaev M, Gadda F, Thomas C, Ferreira RH, Gul U, Maruccia S, Kanbur A, Kinzikeeva E, Abumelha SM, Kosgi R, Gokalp F, Soebadi MA, Paul GM, Sajadi H, Gupte D, Ambar RF, Sogutdelen E, Singla K, Basukarno A, Kim SHK, Gilani MAS, Nagao K, Brodjonegoro SR, Rezano A, Elkhouly M, Mazzilli R, Farsi HMA, Ba HN, Alali H, Kafetzis D, Long TQT, Alsaid S, Cuong HBN, Oleksandr K, Mustafa A, Acosta H, Pai H, Şahin B, Arianto E, Teo C, Jayaprakash SP, Rachman RI, Yenice MG, Sefrioui O, Priyadarshi S, Tanic M, Alfatlaw NK, Rizaldi F, Vishwakarma RB, Kanakis G, Cherian DT, Lee J, Galstyan R, Keskin H, Wurzacher J, Seno DH, Noegroho BS, Margiana R, Javed Q, Castiglioni F, Tanwar R, Puigvert A, Kaya C, Purnomo M, Yazbeck C, Amir A, Borges E, Bellavia M, Deswanto IA, Kv V, Liguori G, Minh DH, Siddiqi K, Colombo F, Zini A, Patel N, Çayan S, Al-Kawaz U, Ragab M, Hebrard GH, de la Rosette J, Efesoy O, Hoffmann I, Teixeira TA, Saylam B, Delgadillo D, and Agarwal A
Abstract: Purpose: Non-obstructive azoospermia (NOA) is a common, but complex problem, with multiple therapeutic options and a lack of clear guidelines. Hence, there is considerable controversy and marked variation in the management of NOA. This survey evaluates contemporary global practices related to medical and surgical management for patients with NOA., Materials and Methods: A 56-question online survey covering various aspects of the evaluation and management of NOA was sent to specialists around the globe. This paper analyzes the results of the second half of the survey dealing with the management of NOA. Results have been compared to current guidelines, and expert recommendations have been provided using a Delphi process., Results: Participants from 49 countries submitted 336 valid responses. Hormonal therapy for 3 to 6 months was suggested before surgical sperm retrieval (SSR) by 29.6% and 23.6% of participants for normogonadotropic hypogonadism and hypergonadotropic hypogonadism respectively. The SSR rate was reported as 50.0% by 26.0% to 50.0% of participants. Interestingly, 46.0% reported successful SSR in <10% of men with Klinefelter syndrome and 41.3% routinely recommended preimplantation genetic testing. Varicocele repair prior to SSR is recommended by 57.7%. Half of the respondents (57.4%) reported using ultrasound to identify the most vascularized areas in the testis for SSR. One-third proceed directly to microdissection testicular sperm extraction (mTESE) in every case of NOA while others use a staged approach. After a failed conventional TESE, 23.8% wait for 3 months, while 33.1% wait for 6 months before proceeding to mTESE. The cut-off of follicle-stimulating hormone for positive SSR was reported to be 12-19 IU/mL by 22.5% of participants and 20-40 IU/mL by 27.8%, while 31.8% reported no upper limit., Conclusions: This is the largest survey to date on the real-world medical and surgical management of NOA by reproductive experts. It demonstrates a diverse practice pattern and highlights the need for evidence-based international consensus guidelines., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)
Published: 2024
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15. Does Varicocele Repair Improve Conventional Semen Parameters? A Meta-Analytic Study of Before-After Data.

Author: Cannarella R, Shah R, Hamoda TAA, Boitrelle F, Saleh R, Gul M, Rambhatla A, Kavoussi P, Toprak T, Harraz AM, Ko E, Çeker G, Durairajanayagam D, Alkahidi N, Kuroda S, Crafa A, Henkel R, Salvio G, Hazir B, Darbandi M, Bendayan M, Darbandi S, Falcone M, Garrido N, Kosgi R, Sawaid Kaiyal R, Karna K, Phuoc NHV, Birowo P, Colpi GM, de la Rosette J, Pinggera GM, Nguyen Q, Zini A, Zohdy W, Singh R, Saini P, Glina S, Lin H, Mostafa T, Rojas-Cruz C, Arafa M, Calogero AE, Dimitriadis F, Kothari P, Karthikeyan VS, Okada K, Chiba K, Kadıoglu A, Altay B, Turunc T, Zilaitiene B, Gokalp F, Adamyan A, Katz D, Chung E, Mierzwa TC, Zylbersztejn DS, Paul GM, Sofikitis N, Sokolakis I, Malhotra V, Brodjonegoro SR, Adriansjah R, Tsujimura A, Amano T, Balercia G, Ziouziou I, Deswanto IA, Martinez M, Park HJ, Bakırcıoglu ME, Ceyhan E, Aydos K, Ramsay J, Minhas S, Al Hashimi M, Ghayda RA, Tadros N, Sindhwani P, Ho CCK, Rachman RI, Rodriguez Pena M, Motawi A, Ponnusamy AK, Dipankar S, Amir A, Binsaleh S, Serefoglu EC, Banthia R, Khalafalla K, Basukarno A, Bac NH, Singla K, Ambar RF, Makarounis K, Priyadarshi S, Duarsa GWK, Atmoko W, Jindal S, Arianto E, Akhavizadegan H, El Bardisi H, Shoshany O, Busetto GM, Moussa M, Jamali M, Al-Marhoon MS, Ruzaev M, Farsi HMA, Mutambirwa S, Lee DS, Kulaksiz D, Cheng YS, Bouzouita A, Sarikaya S, Kandil H, Tsampoukas G, Farkouh A, Bowa K, Savira M, Mogharabian N, Le TV, Harjanggi M, Anh DT, Long TQT, Soebadi MA, Hakim L, Tanic M, Ari UC, Parikh FR, Calik G, Kv V, Dorji G, Rezano A, Rajmil O, Tien DMB, Yuan Y, Lizarraga-Salas JF, Eze B, Ngoo KS, Lee J, Arslan U, and Agarwal A
Abstract: Purpose: The purpose of this meta-analysis is to study the impact of varicocele repair in the largest cohort of infertile males with clinical varicocele by including all available studies, with no language restrictions, comparing intra-person conventional semen parameters before and after the repair of varicoceles., Materials and Methods: The meta-analysis was performed according to PRISMA-P and MOOSE guidelines. A systematic search was performed in Scopus, PubMed, Cochrane, and Embase databases. Eligible studies were selected according to the PICOS model (Population: infertile male patients with clinical varicocele; Intervention: varicocele repair; Comparison: intra-person before-after varicocele repair; Outcome: conventional semen parameters; Study type: randomized controlled trials [RCTs], observational and case-control studies)., Results: Out of 1,632 screened abstracts, 351 articles (23 RCTs, 292 observational, and 36 case-control studies) were included in the quantitative analysis. The before-and-after analysis showed significant improvements in all semen parameters after varicocele repair (except sperm vitality); semen volume: standardized mean difference (SMD) 0.203, 95% CI: 0.129-0.278; p<0.001; I²=83.62%, Egger's p=0.3329; sperm concentration: SMD 1.590, 95% CI: 1.474-1.706; p<0.001; I²=97.86%, Egger's p<0.0001; total sperm count: SMD 1.824, 95% CI: 1.526-2.121; p<0.001; I²=97.88%, Egger's p=0.0063; total motile sperm count: SMD 1.643, 95% CI: 1.318-1.968; p<0.001; I²=98.65%, Egger's p=0.0003; progressive sperm motility: SMD 1.845, 95% CI: 1.537%-2.153%; p<0.001; I²=98.97%, Egger's p<0.0001; total sperm motility: SMD 1.613, 95% CI 1.467%-1.759%; p<0.001; l2=97.98%, Egger's p<0.001; sperm morphology: SMD 1.066, 95% CI 0.992%-1.211%; p<0.001; I²=97.87%, Egger's p=0.1864., Conclusions: The current meta-analysis is the largest to date using paired analysis on varicocele patients. In the current meta-analysis, almost all conventional semen parameters improved significantly following varicocele repair in infertile patients with clinical varicocele., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)
Published: 2024
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16. EGFR mutation testing from pleural effusions of non-small cell lung cancer patients at the institute for oncology and radiology of Serbia.

Author: Vukovic M, Tanic M, Damjanovic A, Pavlovic M, Stanojevic A, Zivic K, Karadzic V, Jankovic R, and Cavic M
Abstract: Background: The use tumor-derived cell-free DNA extracted from body fluids is being evaluated for genetic testing in lung cancer. The aim of this study was to explore the feasibility and utility of implementation of EGFR molecular testing from pleural effusions in non-small cell lung cancer in the clinical diagnostics workflow., Patients and Methods: This study included patients diagnosed with primary lung adenocarcinoma in the period July 2016 to June 2023. EGFR mutation testing was performed by qPCR (Cobas®) and dPCR. Testing was performed from 211 plasma samples when tissue was unavailable at diagnosis, and from 301 plasma samples and 18 pleural effusions at progression on first/second generation of EGFR TKIs. Descriptive methods of statistical analysis were used to summarize the sample data. Fisher's exact test, McNemar's test, Cohen's kappa tests were used for statistical analyses. Two-sided p-values <0.05 were considered statistically significant., Results: A significantly higher detection rate of the T790M mutation in pleural effusion was obtained compared to blood (50% and 20%, p=0.047). When comparing the detection success rate of the resistant T790M mutation in pleural effusion and blood, a statistically significant difference was obtained in favor of pleural effusion (50% vs. 21.87%, p=0.01)., Conclusions: Superior performance of pleural effusions compared to blood plasma was shown both in the analysis of success rate and in the detection of the resistant T790M mutation, at progression on EGFR TKIs. Pleural effusion should be considered in this setting whenever available, especially in countries with limited health resources., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)
Published: 2023
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17. Centrally acting ACE inhibitor (cACEi) and angiotensin receptor blocker (cARB) use and cognitive dysfunction in patients with SLE.

Author: Dobrowolski C, Barraclough M, Su J, Tanic M, Bingham K, Ruttan L, Beaton D, Wither J, Tartaglia MC, Sano M, Kakvan M, Bonilla D, Green R, and Touma Z
Subjects: Humans, Animals, Mice, Angiotensin-Converting Enzyme Inhibitors adverse effects, Ramipril, Angiotensin Receptor Antagonists adverse effects, Retrospective Studies, Lupus Erythematosus, Systemic complications, Lupus Erythematosus, Systemic drug therapy, Cognitive Dysfunction drug therapy, Cognitive Dysfunction etiology
Abstract: Objective: Cognitive dysfunction (CD) is detectable in approximately 40% of patients with SLE. Despite this high prevalence, there are no approved pharmacological treatment options for this detrimental condition. Preliminary murine studies show potential for targeting microglial activation as a treatment of SLE-CD, which may be ameliorated with centrally acting ACE inhibitor (cACEi) and angiotensin receptor blocker (cARB) use. The aim of this study is to determine if there is an association of cACEi/cARB use with cognitive function in a human SLE cohort., Methods: The American College of Rheumatology neuropsychological battery was administered to patients with consecutive SLE at a single academic health centre at baseline, 6 and 12 months. Scores were compared with sex-matched and age-matched control subjects. Clinical and demographic data were gathered at each visit. The primary outcome was CD defined as dysfunction in two or more cognitive domains. The primary predictor was a total cumulative dose of cACEi/cARB in milligrams per kilogram, recorded as an equivalent ramipril dose. Odds of CD with respect to cACEi/cARB use were determined through generalised linear mixed modelling., Results: A total of 300 patients, representing 676 visits, completed this study. One hundred sixteen (39%) met the criteria for CD. Fifty-three participants (18%) were treated with a cACEi or cARB. Mean cumulative dose was 236 mg/kg (calculated as equivalent ramipril dose). Cumulative cACEi/cARB dose was not protective against SLE-CD. Caucasian ethnicity, current employment status and azathioprine cumulative dose were each associated with reduced odds of SLE-CD. Increasing Fatigue Severity Scale score was associated with increased odds of CD., Conclusions: In a single-centre SLE cohort, cACEi/cARB use was not associated with absence of CD. Many important confounders may have influenced the results of this retrospective study. A randomised trial is required to accurately determine if cACEi/cARB is a potential treatment for SLE-CD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Published: 2023
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1. Mixed responses to targeted therapy driven by chromosomal instability through p53 dysfunction and genome doubling

2. The artificial intelligence-based model ANORAK improves histopathological grading of lung adenocarcinoma

3. Body composition and lung cancer-associated cachexia in TRACERx

4. Evolutionary characterization of lung adenocarcinoma morphology in TRACERx

5. Genomic–transcriptomic evolution in lung cancer and metastasis

6. Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA

7. Antibodies against endogenous retroviruses promote lung cancer immunotherapy

8. The evolution of lung cancer and impact of subclonal selection in TRACERx

9. 93P Circulating cell-free DNA fragmentation profiles during systemic therapy of advanced-stage non-small cell lung cancer patients

10. 953P EGFR mutation testing from pleural effusions of advanced lung adenocarcinoma patients in Serbia

11. 28P Identification of convergent gene repression mechanisms through integrative genomic and DNA methylation analysis in NSCLC

12. Two Decades of Progress in Personalized Medicine of Colorectal Cancer in Serbia-Insights from the Institute for Oncology and Radiology of Serbia.

13. Global Practice Patterns in the Evaluation of Non-Obstructive Azoospermia: Results of a World-Wide Survey and Expert Recommendations.

14. Global Practice Patterns and Variations in the Medical and Surgical Management of Non-Obstructive Azoospermia: Results of a World-Wide Survey, Guidelines and Expert Recommendations.

15. Does Varicocele Repair Improve Conventional Semen Parameters? A Meta-Analytic Study of Before-After Data.

16. EGFR mutation testing from pleural effusions of non-small cell lung cancer patients at the institute for oncology and radiology of Serbia.

17. Centrally acting ACE inhibitor (cACEi) and angiotensin receptor blocker (cARB) use and cognitive dysfunction in patients with SLE.

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