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3. Obesity-associated changes in molecular biology of primary breast cancer

Author

Nguyen, Ha-Linh, Geukens, Tatjana, Maetens, Marion, Aparicio, Samuel, Bassez, Ayse, Borg, Ake, Brock, Jane, Broeks, Annegien, Caldas, Carlos, Cardoso, Fatima, De Schepper, Maxim, Delorenzi, Mauro, Drukker, Caroline A., Glas, Annuska M., Green, Andrew R., Isnaldi, Edoardo, Eyfjörð, Jórunn, Khout, Hazem, Knappskog, Stian, Krishnamurthy, Savitri, Lakhani, Sunil R., Langerod, Anita, Martens, John W. M., McCart Reed, Amy E., Murphy, Leigh, Naulaerts, Stefan, Nik-Zainal, Serena, Nevelsteen, Ines, Neven, Patrick, Piccart, Martine, Poncet, Coralie, Punie, Kevin, Purdie, Colin, Rakha, Emad A., Richardson, Andrea, Rutgers, Emiel, Vincent-Salomon, Anne, Simpson, Peter T., Schmidt, Marjanka K., Sotiriou, Christos, Span, Paul N., Tan, Kiat Tee Benita, Thompson, Alastair, Tommasi, Stefania, Van Baelen, Karen, Van de Vijver, Marc, Van Laere, Steven, van’t Veer, Laura, Viale, Giuseppe, Viari, Alain, Vos, Hanne, Witteveen, Anke T., Wildiers, Hans, Floris, Giuseppe, Garg, Abhishek D., Smeets, Ann, Lambrechts, Diether, Biganzoli, Elia, Richard, François, and Desmedt, Christine

Published
2023
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5. Whole Genome Sequencing in Advanced Lung Cancer can be Performed Using Diff-Quik Cytology Smears Derived from Endobronchial Ultrasound, Transbronchial Needle Aspiration (EBUS TBNA)

Author

Fielding, David, Dalley, Andrew J., Singh, Mahendra, Nandakumar, Lakshmy, Lakis, Vanessa, Chittoory, Haarika, Fairbairn, David, Ferguson, Kaltin, Bashirzadeh, Farzad, Bint, Michael, Pahoff, Carl, Son, Jung Hwa, Hodgson, Alan, Pearson, John V., Waddell, Nicola, Lakhani, Sunil R., Hartel, Gunter, Nones, Katia, and Simpson, Peter T.

Published
2023
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6. Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer

Author

Tutt, Andrew NJ, Garber, Judy E, Kaufman, Bella, Viale, Giuseppe, Fumagalli, Debora, Rastogi, Priya, Gelber, Richard D, de Azambuja, Evandro, Fielding, Anitra, Balmaña, Judith, Domchek, Susan M, Gelmon, Karen A, Hollingsworth, Simon J, Korde, Larissa A, Linderholm, Barbro, Bandos, Hanna, Senkus, Elżbieta, Suga, Jennifer M, Shao, Zhimin, Pippas, Andrew W, Nowecki, Zbigniew, Huzarski, Tomasz, Ganz, Patricia A, Lucas, Peter C, Baker, Nigel, Loibl, Sibylle, McConnell, Robin, Piccart, Martine, Schmutzler, Rita, Steger, Guenther G, Costantino, Joseph P, Arahmani, Amal, Wolmark, Norman, McFadden, Eleanor, Karantza, Vassiliki, Lakhani, Sunil R, Yothers, Greg, Campbell, Christine, and Geyer, Charles E

Subjects
Digestive Diseases, Breast Cancer, Cancer, Clinical Research, Clinical Trials and Supportive Activities, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Good Health and Well Being, Adult, Antineoplastic Agents, Breast Neoplasms, Chemotherapy, Adjuvant, Disease-Free Survival, Double-Blind Method, Female, Genes, BRCA1, Genes, BRCA2, Germ-Line Mutation, Humans, Mastectomy, Middle Aged, Phthalazines, Piperazines, Poly(ADP-ribose) Polymerase Inhibitors, Receptor, ErbB-2, OlympiA Clinical Trial Steering Committee and Investigators, Receptor, erbB-2, Medical and Health Sciences, General & Internal Medicine
Abstract

BackgroundPoly(adenosine diphosphate-ribose) polymerase inhibitors target cancers with defects in homologous recombination repair by synthetic lethality. New therapies are needed to reduce recurrence in patients with BRCA1 or BRCA2 germline mutation-associated early breast cancer.MethodsWe conducted a phase 3, double-blind, randomized trial involving patients with human epidermal growth factor receptor 2 (HER2)-negative early breast cancer with BRCA1 or BRCA2 germline pathogenic or likely pathogenic variants and high-risk clinicopathological factors who had received local treatment and neoadjuvant or adjuvant chemotherapy. Patients were randomly assigned (in a 1:1 ratio) to 1 year of oral olaparib or placebo. The primary end point was invasive disease-free survival.ResultsA total of 1836 patients underwent randomization. At a prespecified event-driven interim analysis with a median follow-up of 2.5 years, the 3-year invasive disease-free survival was 85.9% in the olaparib group and 77.1% in the placebo group (difference, 8.8 percentage points; 95% confidence interval [CI], 4.5 to 13.0; hazard ratio for invasive disease or death, 0.58; 99.5% CI, 0.41 to 0.82; P

Published
2021

7. Cancer Risks Associated With TP53 Pathogenic Variants: Maximum Likelihood Analysis of Extended Pedigrees for Diagnosis of First Cancers Beyond the Li-Fraumeni Syndrome Spectrum

Author

Fortuno, Cristina, Feng, Bing-Jian, Carroll, Courtney, Innella, Giovanni, Kohlmann, Wendy, Lázaro, Conxi, Brunet, Joan, Feliubadaló, Lidia, Iglesias, Silvia, Menéndez, Mireia, Teulé, Alex, Ballinger, Mandy L., Thomas, David M., Campbell, Ainsley, Field, Mike, Harris, Marion, Kirk, Judy, Pachter, Nicholas, Poplawski, Nicola, Susman, Rachel, Tucker, Kathy, Wallis, Mathew, Williams, Rachel, Cops, Elisa, Goldgar, David, James, Paul A., Spurdle, Amanda B., Amor, David, Andrews, Lesley, Antill, Yoland, Balleine, Rosemary, Beesley, Jonathan, Bennett, Ian, Bogwitz, Michael, Bodek, Simon, Botes, Leon, Brennan, Meagan, Brown, Melissa, Buckley, Michael, Burke, Jo, Butow, Phyllis, Caldon, Liz, Campbell, Ian, Cao, Michelle, Chakrabarti, Anannya, Chauhan, Deepa, Chauhan, Manisha, Chenevix-Trench, Georgia, Christian, Alice, Cohen, Paul, Colley, Alison, Crook, Ashley, Cui, James, Courtney, Eliza, Cummings, Margaret, Dawson, Sarah-Jane, deFazio, Anna, Delatycki, Martin, Dickson, Rebecca, Dixon, Joanne, Edkins, Ted, Edwards, Stacey, Farshid, Gelareh, Fellows, Andrew, Fenton, Georgina, Field, Michael, Flanagan, James, Fong, Peter, Forrest, Laura, Fox, Stephen, French, Juliet, Friedlander, Michael, Gaff, Clara, Gattas, Mike, George, Peter, Greening, Sian, Harris, Marion, Hart, Stewart, Hayward, Nick, Hopper, John, Hoskins, Cass, Hunt, Clare, James, Paul, Jenkins, Mark, Kidd, Alexa, Kirk, Judy, Koehler, Jessica, Kollias, James, Lakhani, Sunil, Lawrence, Mitchell, Lee, Jason, Li, Shuai, Lindeman, Geoff, Lippey, Jocelyn, Lipton, Lara, Lobb, Liz, Loi, Sherene, Mann, Graham, Marsh, Deborah, McLachlan, Sue Anne, Meiser, Bettina, Milne, Roger, Nightingale, Sophie, OʼConnell, Shona, OʼSullivan, Sarah, Ortega, David Gallego, Pachter, Nick, Pang, Jia-Min, Pathak, Gargi, Patterson, Briony, Pearn, Amy, Phillips, Kelly, Pieper, Ellen, Ramus, Susan, Rickard, Edwina, Robinson, Bridget, Saleh, Mona, Skandarajah, Anita, Salisbury, Elizabeth, Saunders, Christobel, Saunus, Jodi, Savas, Peter, Scott, Rodney, Scott, Clare, Sexton, Adrienne, Shaw, Joanne, Shelling, Andrew, Srinivasa, Shweta, Simpson, Peter, Southey, Melissa, Spurdle, Amanda, Taylor, Jessica, Taylor, Renea, Thorne, Heather, Trainer, Alison, Tucker, Kathy, Visvader, Jane, Walker, Logan, Williams, Rachael, Winship, Ingrid, Young, Mary Ann, and Zaheed, Milita

Published
2024
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8. The impact of coding germline variants on contralateral breast cancer risk and survival

Author

Sahlberg, Kristine K., Børresen-Dale, Anne-Lise, Gram, Inger Torhild, Olsen, Karina Standahl, Engebråten, Olav, Naume, Bjørn, Geisler, Jürgen, OSBREAC, Grenaker Alnæs, Grethe I., Amor, David, Andrews, Lesley, Antill, Yoland, Balleine, Rosemary, Beesley, Jonathan, Bennett, Ian, Bogwitz, Michael, Botes, Leon, Brennan, Meagan, Brown, Melissa, Buckley, Michael, Burke, Jo, Butow, Phyllis, Caldon, Liz, Campbell, Ian, Cao, Michelle, Chakrabarti, Anannya, Chauhan, Deepa, Chauhan, Manisha, Chenevix-Trench, Georgia, Christian, Alice, Cohen, Paul, Colley, Alison, Crook, Ashley, Cui, James, Courtney, Eliza, Cummings, Margaret, Dawson, Sarah-Jane, DeFazio, Anna, Delatycki, Martin, Dickson, Rebecca, Dixon, Joanne, Edkins, Ted, Edwards, Stacey, Farshid, Gelareh, Fellows, Andrew, Fenton, Georgina, Field, Michael, Flanagan, James, Fong, Peter, Forrest, Laura, Fox, Stephen, French, Juliet, Friedlander, Michael, Gaff, Clara, Gattas, Mike, George, Peter, Greening, Sian, Harris, Marion, Hart, Stewart, Hayward, Nick, Hopper, John, Hoskins, Cass, Hunt, Clare, James, Paul, Jenkins, Mark, Kidd, Alexa, Kirk, Judy, Koehler, Jessica, Kollias, James, Lakhani, Sunil, Lawrence, Mitchell, Lee, Jason, Li, Shuai, Lindeman, Geoff, Lipton, Lara, Lobb, Liz, Loi, Sherene, Mann, Graham, Marsh, Deborah, McLachlan, Sue Anne, Meiser, Bettina, Milne, Roger, Nightingale, Sophie, O'Connell, Shona, O'Sullivan, Sarah, Ortega, David Gallego, Pachter, Nick, Pang, Jia-Min, Pathak, Gargi, Patterson, Briony, Pearn, Amy, Phillips, Kelly, Pieper, Ellen, Ramus, Susan, Rickard, Edwina, Robinson, Bridget, Saleh, Mona, Skandarajah, Anita, Salisbury, Elizabeth, Saunders, Christobel, Saunus, Jodi, Scott, Rodney, Scott, Clare, Sexton, Adrienne, Shelling, Andrew, Simpson, Peter, Southey, Melissa, Spurdle, Amanda, Taylor, Jessica, Taylor, Renea, Thorne, Heather, Trainer, Alison, Tucker, Kathy, Visvader, Jane, Walker, Logan, Williams, Rachael, Winship, Ingrid, Young, Mary Ann, Zaheed, Milita, Morra, Anna, Mavaddat, Nasim, Muranen, Taru A., Ahearn, Thomas U., Allen, Jamie, Andrulis, Irene L., Auvinen, Päivi, Becher, Heiko, Behrens, Sabine, Blomqvist, Carl, Bojesen, Stig E., Bolla, Manjeet K., Brauch, Hiltrud, Camp, Nicola J., Carvalho, Sara, Castelao, Jose E., Cessna, Melissa H., Chang-Claude, Jenny, Czene, Kamila, Decker, Brennan, Dennis, Joe, Dörk, Thilo, Dorling, Leila, Dunning, Alison M., Ekici, Arif B., Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine D., Flyger, Henrik, Gago-Dominguez, Manuela, García-Closas, Montserrat, Geurts-Giele, Willemina R.R., Giles, Graham G., Guénel, Pascal, Gündert, Melanie, Hahnen, Eric, Hall, Per, Hamann, Ute, Harrington, Patricia A., He, Wei, Heikkilä, Päivi, Hooning, Maartje J., Hoppe, Reiner, Howell, Anthony, Humphreys, Keith, Jakubowska, Anna, Jung, Audrey Y., Keeman, Renske, Kristensen, Vessela N., Lubiński, Jan, Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Mavroudis, Dimitrios, Milne, Roger L., Mulligan, Anna Marie, Newman, William G., Park-Simon, Tjoung-Won, Peterlongo, Paolo, Pharoah, Paul D.P., Rhenius, Valerie, Saloustros, Emmanouil, Sawyer, Elinor J., Schmutzler, Rita K., Shah, Mitul, Spurdle, Amanda B., Tomlinson, Ian, Truong, Thérèse, van Veen, Elke M., Vreeswijk, Maaike P.G., Wang, Qin, Wendt, Camilla, Yang, Xiaohong R., Nevanlinna, Heli, Devilee, Peter, Easton, Douglas F., and Schmidt, Marjanka K.

Published
2023
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11. Prospective Optimization of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration Lymph Node Assessment for Lung Cancer: Three Needle Agitations Are Noninferior to 10 Agitations for Adequate Tumor Cell and DNA Yield

Author

Fielding, David, Dalley, Andrew J., Singh, Mahendra, Nandakumar, Lakshmy, Nones, Katia, Lakis, Vanessa, Chittoory, Haarika, Ferguson, Kaltin, Bashirzadeh, Farzad, Bint, Michael, Pahoff, Carl, Son, Jung Hwa, Hodgson, Alan, Sharma, Sowmya, Godbolt, David, Coleman, Kylie, Whitfield, Lenore, Waddell, Nicola, Lakhani, Sunil R., Hartel, Gunter, and Simpson, Peter T.

Published
2022
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12. Epigenome erosion and SOX10 drive neural crest phenotypic mimicry in triple-negative breast cancer

Author

Saunus, Jodi M., De Luca, Xavier M., Northwood, Korinne, Raghavendra, Ashwini, Hasson, Alexander, McCart Reed, Amy E., Lim, Malcolm, Lal, Samir, Vargas, A. Cristina, Kutasovic, Jamie R., Dalley, Andrew J., Miranda, Mariska, Kalaw, Emarene, Kalita-de Croft, Priyakshi, Gresshoff, Irma, Al-Ejeh, Fares, Gee, Julia M. W., Ormandy, Chris, Khanna, Kum Kum, Beesley, Jonathan, Chenevix-Trench, Georgia, Green, Andrew R., Rakha, Emad A., Ellis, Ian O., Nicolau, Jr, Dan V., Simpson, Peter T., and Lakhani, Sunil R.

Published
2022
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15. Mapping the cited evidence of ductal carcinoma in situ from the 5th edition of the World Health Organisation classification of tumours of the breast.

Author

Wong, Clarissa Jing Wen, Md Nasir, Nur Diyana, Koh, Valerie Cui Yun, Campbell, Fiona, Fox, Stephen, Lakhani, Sunil R, Myles, Nickolas, Yip, George, Colling, Richard, Cree, Ian A, Lokuhetty, Dilani, and Tan, Puay Hoon

Subjects
CARCINOMA in situ, DUCTAL carcinoma, MOLECULAR pathology, ETIOLOGY of diseases, SCIENTIFIC observation, BREAST
Abstract

Aims: Ductal carcinoma in situ (DCIS) is recognised by the World Health Organisation (WHO) Classification of Tumours (WCT) as a non‐invasive neoplastic epithelial proliferation confined to the mammary ducts and lobules. This report categorises the references cited in the DCIS chapter of the 5th edition of the WCT (Breast Tumours) according to prevailing evidence levels for evidence‐based medicine and the Hierarchy of Evidence for Tumour Pathology (HETP), identifying potential gaps that can inform subsequent editions of the WCT for this tumour. Methods and results: We included all citations from the DCIS chapter of the WCT (Breast Tumours, 5th edition). Each citation was appraised according to its study design and evidence level. We developed our map of cited evidence, which is a graphical matrix of tumour type (column) and tumour descriptors (rows). Spheres were used to represent the evidence, with size and colour corresponding to their number and evidence level respectively. Thirty‐six publications were retrieved. The cited literature in the DCIS chapter comprised mainly case series and were regarded as low‐level. We found an unequal distribution of citations among tumour descriptors. 'Pathogenesis' and 'prognosis and prediction' contained the most references, while 'clinical features', 'aetiology' and 'diagnostic molecular pathology' had only a single citation each. 'Prognosis and prediction' had the greatest proportion of moderate‐ and high‐levels of evidence. Conclusion: Our findings align with the disposition for observational studies inherent in the field of pathology. Our map is a springboard for future efforts in mapping all available evidence on DCIS, potentially augmenting the editorial process and future editions of WCTs. [ABSTRACT FROM AUTHOR]

Published
2024
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16. Dataset for reporting of the invasive carcinoma of the breast: recommendations from the International Collaboration on Cancer Reporting (ICCR).

Author

Ellis, Ian, Webster, Fleur, Allison, Kimberly H, Dang, Chau, Gobbi, Helenice, Kulka, Janina, Lakhani, Sunil R, Moriya, Takuya, Quinn, Cecily M, Sapino, Anna, Schnitt, Stuart, Sibbering, D Mark, Slodkowska, Elzbieta, Yang, Wentao, and Tan, Puay H

Subjects
CANCER invasiveness, BREAST cancer, CANCER patients, PATHOLOGISTS, PATHOLOGY, BREAST
Abstract

Background and Objectives: Current national or regional guidelines for the pathology reporting on invasive breast cancer differ in certain aspects, resulting in divergent reporting practice and a lack of comparability of data. Here we report on a new international dataset for the pathology reporting of resection specimens with invasive cancer of the breast. The dataset was produced under the auspices of the International Collaboration on Cancer Reporting (ICCR), a global alliance of major (inter‐)national pathology and cancer organizations. Methods and Results: The established ICCR process for dataset development was followed. An international expert panel consisting of breast pathologists, a surgeon, and an oncologist prepared a draft set of core and noncore data items based on a critical review and discussion of current evidence. Commentary was provided for each data item to explain the rationale for selecting it as a core or noncore element, its clinical relevance, and to highlight potential areas of disagreement or lack of evidence, in which case a consensus position was formulated. Following international public consultation, the document was finalized and ratified, and the dataset, which includes a synoptic reporting guide, was published on the ICCR website. Conclusions: This first international dataset for invasive cancer of the breast is intended to promote high‐quality, standardized pathology reporting. Its widespread adoption will improve consistency of reporting, facilitate multidisciplinary communication, and enhance comparability of data, all of which will help to improve the management of invasive breast cancer patients. [ABSTRACT FROM AUTHOR]

Published
2024
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17. Predictive biomarkers of breast ductal carcinoma in situ may underestimate the risk of recurrence due to de novo ipsilateral breast carcinoma development

Author

Kader, Tanjina, primary, Zethoven, Maia, additional, Mahale, Sakshi, additional, Saunders, Hugo, additional, Tjoeka, Lauren, additional, Lehmann, Rebecca, additional, Jayawardane, Madawa, additional, Pang, Jia-Min, additional, Lesche, Dorothea, additional, Rajan, Neeha, additional, Semple, Timothy, additional, Lee, Jue Er Amanda, additional, Lupat, Richard, additional, Byrne, David J, additional, Hughes, Siobhan, additional, Nguyen, Hoa, additional, Lai, Siqi, additional, Pechlivanis, Maree, additional, Craig, Olivia, additional, Devereux, Lisa, additional, House, Eloise, additional, Jayasinghe, Sureshni I, additional, Kaufmann, Tom L, additional, Schwarz, Roland F, additional, Green, Andrew R, additional, Miligy, Islam, additional, Cummings, Margaret, additional, Lakhani, Sunil, additional, Campbell, Ian G, additional, Rakha, Emad, additional, Fox, Stephen B, additional, Mann, G Bruce, additional, and Gorringe, Kylie L, additional

Published
2024
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18. B7-H3 Expression in Breast Cancer and Brain Metastasis

Author

Joshi, Vaibhavi, primary, Beecher, Kate, additional, Lim, Malcolm, additional, Stacey, Andrew, additional, Feng, Yufan, additional, Jat, Parmjit S., additional, Duijf, Pascal H. G., additional, Simpson, Peter T., additional, Lakhani, Sunil R., additional, and McCart Reed, Amy E., additional

Published
2024
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19. A dedicated structured data set for reporting of invasive carcinoma of the breast in the setting of neoadjuvant therapy: recommendations from the International Collaboration on Cancer Reporting (ICCR)

Author

Bossuyt, Veerle, primary, Provenzano, Elena, additional, Symmans, W Fraser, additional, Webster, Fleur, additional, Allison, Kimberly H, additional, Dang, Chau, additional, Helenice, Gobbi, additional, Kulka, Janina, additional, Lakhani, Sunil R, additional, Moriya, Takuya, additional, Quinn, Cecily M, additional, Sapino, Anna, additional, Schnitt, Stuart, additional, Sibbering, D Mark, additional, Slodkowska, Elzbieta, additional, Yang, Wentao, additional, Tan, Puay Hoon, additional, and Ellis, Ian, additional

Published
2024
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20. Columnar Cell Lesions

Author

Cummings, Margaret C., Simpson, Peter T., Lakhani, Sunil R., van Krieken, J. H. J. M., Series Editor, Sapino, Anna, editor, and Kulka, Janina, editor

Published
2020
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21. Somatic mutations reveal asymmetric cellular dynamics in the early human embryo.

Author

Ju, Young Seok, Martincorena, Inigo, Gerstung, Moritz, Petljak, Mia, Alexandrov, Ludmil B, Rahbari, Raheleh, Wedge, David C, Davies, Helen R, Ramakrishna, Manasa, Fullam, Anthony, Martin, Sancha, Alder, Christopher, Patel, Nikita, Gamble, Steve, O'Meara, Sarah, Giri, Dilip D, Sauer, Torril, Pinder, Sarah E, Purdie, Colin A, Borg, Åke, Stunnenberg, Henk, van de Vijver, Marc, Tan, Benita KT, Caldas, Carlos, Tutt, Andrew, Ueno, Naoto T, van 't Veer, Laura J, Martens, John WM, Sotiriou, Christos, Knappskog, Stian, Span, Paul N, Lakhani, Sunil R, Eyfjörd, Jórunn Erla, Børresen-Dale, Anne-Lise, Richardson, Andrea, Thompson, Alastair M, Viari, Alain, Hurles, Matthew E, Nik-Zainal, Serena, Campbell, Peter J, and Stratton, Michael R

Subjects
Blood Cells, Humans, Mutagenesis, Cell Lineage, Embryonic Development, Mutation, Mosaicism, Germ-Line Mutation, Genome, Human, Adult, Embryo, Mammalian, Mutation Rate, Embryo, Mammalian, Genome, Human, General Science & Technology
Abstract

Somatic cells acquire mutations throughout the course of an individual's life. Mutations occurring early in embryogenesis are often present in a substantial proportion of, but not all, cells in postnatal humans and thus have particular characteristics and effects. Depending on their location in the genome and the proportion of cells they are present in, these mosaic mutations can cause a wide range of genetic disease syndromes and predispose carriers to cancer. They have a high chance of being transmitted to offspring as de novo germline mutations and, in principle, can provide insights into early human embryonic cell lineages and their contributions to adult tissues. Although it is known that gross chromosomal abnormalities are remarkably common in early human embryos, our understanding of early embryonic somatic mutations is very limited. Here we use whole-genome sequences of normal blood from 241 adults to identify 163 early embryonic mutations. We estimate that approximately three base substitution mutations occur per cell per cell-doubling event in early human embryogenesis and these are mainly attributable to two known mutational signatures. We used the mutations to reconstruct developmental lineages of adult cells and demonstrate that the two daughter cells of many early embryonic cell-doubling events contribute asymmetrically to adult blood at an approximately 2:1 ratio. This study therefore provides insights into the mutation rates, mutational processes and developmental outcomes of cell dynamics that operate during early human embryogenesis.

Published
2017

24. Breast Cancer Heterogeneity in Primary and Metastatic Disease

Author

Kalinowski, Lauren, Saunus, Jodi M., McCart Reed, Amy E., Lakhani, Sunil R., COHEN, IRUN R., Editorial Board Member, LAJTHA, ABEL, Editorial Board Member, LAMBRIS, JOHN D., Editorial Board Member, PAOLETTI, RODOLFO, Editorial Board Member, REZAEI, NIMA, Editorial Board Member, and Ahmad, Aamir, editor

Published
2019
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26. Evaluation of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration (EBUS-TBNA) Samples from Advanced Non-Small Cell Lung Cancer for Whole Genome, Whole Exome and Comprehensive Panel Sequencing

Author

Fielding, David, primary, Lakis, Vanessa, additional, Dalley, Andrew J., additional, Chittoory, Haarika, additional, Newell, Felicity, additional, Koufariotis, Lambros T., additional, Patch, Ann-Marie, additional, Kazakoff, Stephen, additional, Bashirzadeh, Farzad, additional, Son, Jung Hwa, additional, Ryan, Kimberley, additional, Steinfort, Daniel, additional, Williamson, Jonathan P., additional, Bint, Michael, additional, Pahoff, Carl, additional, Nguyen, Phan Tien, additional, Twaddell, Scott, additional, Arnold, David, additional, Grainge, Christopher, additional, Pattison, Andrew, additional, Fairbairn, David, additional, Gune, Shailendra, additional, Christie, Jemma, additional, Holmes, Oliver, additional, Leonard, Conrad, additional, Wood, Scott, additional, Pearson, John V., additional, Lakhani, Sunil R., additional, Waddell, Nicola, additional, Simpson, Peter T., additional, and Nones, Katia, additional

Published
2024
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28. Detailed DNA methylation characterisation of phyllodes tumours identifies a signature of malignancy and distinguishes phyllodes from metaplastic breast carcinoma

Author

Meyer, Braydon, primary, Stirzaker, Clare, additional, Ramkomuth, Sonny, additional, Harvey, Kate, additional, Chan, Belinda, additional, Lee, Cheok Soon, additional, Karim, Rooshdiya, additional, Deng, Niantao, additional, Avery‐Kiejda, Kelly A, additional, Scott, Rodney J, additional, Lakhani, Sunil, additional, Fox, Stephen, additional, Robbins, Elizabeth, additional, Shin, Joo‐Shik, additional, Beith, Jane, additional, Gill, Anthony, additional, Sioson, Loretta, additional, Chan, Charles, additional, Krishnaswamy, Mrudula, additional, Cooper, Caroline, additional, Warrier, Sanjay, additional, Mak, Cindy, additional, Rasko, John EJ, additional, Bailey, Charles G, additional, Swarbrick, Alexander, additional, Clark, Susan J, additional, O'Toole, Sandra, additional, and Pidsley, Ruth, additional

Published
2024
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32. Estrogen and Progesterone Receptor Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Guideline Update

Author

Allison, Kimberly H., Hammond, M. Elizabeth H., Dowsett, Mitchell, McKernin, Shannon E., Carey, Lisa A., Fitzgibbons, Patrick L., Hayes, Daniel F., Lakhani, Sunil R., Chavez-MacGregor, Mariana, Perlmutter, Jane, Perou, Charles M., Regan, Meredith M., Rimm, David L., Symmans, W. Fraser, Torlakovic, Emina E., Varella, Leticia, Viale, Giuseppe, Weisberg, Tracey F., McShane, Lisa M., and Wolff, Antonio C.

Subjects
Merck & Company Inc., Pfizer Inc., Bristol-Myers Squibb Co., AstraZeneca PLC, Ductal carcinoma in situ -- Care and treatment, Cancer prevention, Medical societies, Immunohistochemistry, Medical research, Estrogens, Progesterone, Pharmaceutical industry, Phenols (Class of compounds), Breast cancer, Carcinoma, Tumors, Sex hormones, Setting (Literature), Professional associations, Health, College of American Pathologists
Abstract

* Purpose.--To update key recommendations of the American Society of Clinical Oncology/College of American Pathologists estrogen receptor (ER) and progesterone receptor (PgR) testing in breast cancer guideline. Methods.--A multidisciplinary international Expert Panel was convened to update the clinical practice guideline recommendations informed by a systematic review of the medical literature. Recommendations.--The Expert Panel continues to recommend ER testing of invasive breast cancers by validated immunohistochemistry as the standard for predicting which patients may benefit from endocrine therapy, and no other assays are recommended for this purpose. Breast cancer samples with 1% to 100% of tumor nuclei positive should be interpreted as ER positive. However, the Expert Panel acknowledges that there are limited data on endocrine therapy benefit for cancers with 1% to 10% of cells staining ER positive. Samples with these results should be reported using a new reporting category, ER Low Positive, with a recommended comment. A sample is considered ER negative if < 1% or 0% of tumor cell nuclei are immunoreactive. Additional strategies recommended to promote optimal performance, interpretation, and reporting of cases with an initial low to no ER staining result include establishing a laboratory-specific standard operating procedure describing additional steps used by the laboratory to confirm/adjudicate results. The status of controls should be reported for cases with 0% to 10% staining. Similar principles apply to PgR testing, which is used primarily for prognostic purposes in the setting of an ER-positive cancer. Testing of ductal carcinoma in situ (DCIS) for ER is recommended to determine potential benefit of endocrine therapies to reduce risk of future breast cancer, while testing DCIS for PgR is considered optional. Additional information can be found at www.asco.org/breast-cancer-guidelines. (Arch Pathol Lab Med. 2020;144:545-563; doi: 10.5858/arpa.2019-0904-SA), INTRODUCTION First released in 2010, the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) estrogen receptor (ER) and progesterone receptor (PgR) testing guideline is aimed at improving the [...]

Published
2020
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33. Metaplastic breast cancers frequently express immune checkpoint markers FOXP3 and PD-L1

Author

Kalaw, Emarene, Lim, Malcolm, Kutasovic, Jamie R., Sokolova, Anna, Taege, Lucinda, Johnstone, Kate, Bennett, James, Saunus, Jodi M., Niland, Colleen, Ferguson, Kaltin, Gresshoff, Irma, Bettington, Mark, Pathmanathan, Nirmala, Tse, Gary M., Papadimos, David, Pathmanathan, Rajadurai, Harris, Gavin, Yamaguchi, Rin, Tan, Puay Hoon, Fox, Stephen, O’Toole, Sandra A., Simpson, Peter T., Lakhani, Sunil R., and McCart Reed, Amy E.

Published
2020
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34. Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells

Author

Ju, Young Seok, Tubio, Jose MC, Mifsud, William, Fu, Beiyuan, Davies, Helen R, Ramakrishna, Manasa, Li, Yilong, Yates, Lucy, Gundem, Gunes, Tarpey, Patrick S, Behjati, Sam, Papaemmanuil, Elli, Martin, Sancha, Fullam, Anthony, Gerstung, Moritz, Group, ICGC Prostate Cancer Working, Group, ICGC Bone Cancer Working, Group, ICGC Breast Cancer Working, Nangalia, Jyoti, Green, Anthony R, Caldas, Carlos, Borg, Åke, Tutt, Andrew, Lee, Ming Ta Michael, Veer, Laura J van't, Tan, Benita KT, Aparicio, Samuel, Span, Paul N, Martens, John WM, Knappskog, Stian, Vincent-Salomon, Anne, Børresen-Dale, Anne-Lise, Eyfjörd, Jórunn Erla, Flanagan, Adrienne M, Foster, Christopher, Neal, David E, Cooper, Colin, Eeles, Rosalind, Lakhani, Sunil R, Desmedt, Christine, Thomas, Gilles, Richardson, Andrea L, Purdie, Colin A, Thompson, Alastair M, McDermott, Ultan, Yang, Fengtang, Nik-Zainal, Serena, Campbell, Peter J, and Stratton, Michael R

Subjects
Biochemistry and Cell Biology, Genetics, Biological Sciences, Stem Cell Research - Nonembryonic - Human, Human Genome, Stem Cell Research, Cancer, 1.1 Normal biological development and functioning, Underpinning research, Aetiology, 2.1 Biological and endogenous factors, Generic health relevance, Amino Acid Sequence, Cell Line, Tumor, Cell Nucleus, Chromosomes, DNA Copy Number Variations, DNA End-Joining Repair, DNA Replication, DNA, Mitochondrial, Genome, Human, Genome, Mitochondrial, HeLa Cells, Humans, In Situ Hybridization, Fluorescence, Mitochondria, Molecular Sequence Data, Neoplasms, Reproducibility of Results, Sequence Analysis, DNA, ICGC Prostate Cancer Working Group, ICGC Bone Cancer Working Group, ICGC Breast Cancer Working Group, Hela Cells, Medical and Health Sciences, Bioinformatics
Abstract

Mitochondrial genomes are separated from the nuclear genome for most of the cell cycle by the nuclear double membrane, intervening cytoplasm, and the mitochondrial double membrane. Despite these physical barriers, we show that somatically acquired mitochondrial-nuclear genome fusion sequences are present in cancer cells. Most occur in conjunction with intranuclear genomic rearrangements, and the features of the fusion fragments indicate that nonhomologous end joining and/or replication-dependent DNA double-strand break repair are the dominant mechanisms involved. Remarkably, mitochondrial-nuclear genome fusions occur at a similar rate per base pair of DNA as interchromosomal nuclear rearrangements, indicating the presence of a high frequency of contact between mitochondrial and nuclear DNA in some somatic cells. Transmission of mitochondrial DNA to the nuclear genome occurs in neoplastically transformed cells, but we do not exclude the possibility that some mitochondrial-nuclear DNA fusions observed in cancer occurred years earlier in normal somatic cells.

Published
2015

35. Co-observation of germline pathogenic variants in breast cancer predisposition genes: Results from analysis of the BRIDGES sequencing dataset

Author

Sahlberg, Kristine K., Børresen-Dale, Anne-Lise, Gram, Inger Torhild, Olsen, Karina Standahl, Engebråten, Olav, Naume, Bjørn, Geisler, Jürgen, OSBREAC, Grenaker Alnæs, Grethe I., Amor, David, Andrews, Lesley, Antill, Yoland, Balleine, Rosemary, Beesley, Jonathan, Bennett, Ian, Bogwitz, Michael, Bodek, Simon, Botes, Leon, Brennan, Meagan, Brown, Melissa, Buckley, Michael, Burke, Jo, Butow, Phyllis, Caldon, Liz, Campbell, Ian, Cao, Michelle, Chakrabarti, Anannya, Chauhan, Deepa, Chauhan, Manisha, Christian, Alice, Cohen, Paul, Colley, Alison, Crook, Ashley, Cui, James, Courtney, Eliza, Cummings, Margaret, Dawson, Sarah-Jane, deFazio, Anna, Delatycki, Martin, Dickson, Rebecca, Dixon, Joanne, Edwards, Stacey, Farshid, Gelareh, Fellows, Andrew, Fenton, Georgina, Field, Michael, Flanagan, James, Fong, Peter, Forrest, Laura, Fox, Stephen, French, Juliet, Friedlander, Michael, Gaff, Clara, Gattas, Mike, George, Peter, Greening, Sian, Harris, Marion, Hart, Stewart, Harraka, Philip, Hayward, Nick, Hopper, John, Hoskins, Cass, Hunt, Clare, Jenkins, Mark, Kidd, Alexa, Kirk, Judy, Koehler, Jessica, Kollias, James, Lakhani, Sunil, Lawrence, Mitchell, Lee, Jason, Li, Shuai, Lindeman, Geoff, Lippey, Jocelyn, Lipton, Lara, Lobb, Liz, Loi, Sherene, Mann, Graham, Marsh, Deborah, McLachlan, Sue Anne, Meiser, Bettina, Nightingale, Sophie, O'Connell, Shona, O'Sullivan, Sarah, Ortega, David Gallego, Pachter, Nick, Pang, Jia-Min, Pathak, Gargi, Patterson, Briony, Pearn, Amy, Phillips, Kelly, Pieper, Ellen, Ramus, Susan, Rickard, Edwina, Ragunathan, Abi, Robinson, Bridget, Saleh, Mona, Skandarajah, Anita, Salisbury, Elizabeth, Saunders, Christobel, Saunus, Jodi, Savas, Peter, Scott, Rodney, Scott, Clare, Sexton, Adrienne, Shaw, Joanne, Shelling, Andrew, Srinivasa, Shweta, Simpson, Peter, Taylor, Jessica, Taylor, Renea, Thorne, Heather, Trainer, Alison, Tucker, Kathy, Visvader, Jane, Walker, Logan, Williams, Rachael, Winship, Ingrid, Young, Mary Ann, Zaheed, Milita, Davidson, Aimee L., Michailidou, Kyriaki, Parsons, Michael T., Fortuno, Cristina, Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Naven, Marc, Abubakar, Mustapha, Ahearn, Thomas U., Alonso, M. Rosario, Andrulis, Irene L., Antoniou, Antonis C., Auvinen, Päivi, Behrens, Sabine, Bermisheva, Marina A., Bogdanova, Natalia V., Bojesen, Stig E., Brüning, Thomas, Byers, Helen J., Camp, Nicola J., Campbell, Archie, Castelao, Jose E., Cessna, Melissa H., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Collée, J. Margriet, Czene, Kamila, Dörk, Thilo, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine D., Flyger, Henrik, Gago-Dominguez, Manuela, García-Closas, Montserrat, Glendon, Gord, González-Neira, Anna, Grassmann, Felix, Gronwald, Jacek, Guénel, Pascal, Hadjisavvas, Andreas, Haeberle, Lothar, Hall, Per, Hamann, Ute, Hartman, Mikael, Ho, Peh Joo, Hooning, Maartje J., Hoppe, Reiner, Howell, Anthony, Jakubowska, Anna, Khusnutdinova, Elza K., Kristensen, Vessela N., Li, Jingmei, Lim, Joanna, Lindblom, Annika, Liu, Jenny, Lophatananon, Artitaya, Mannermaa, Arto, Mavroudis, Dimitrios A., Mensenkamp, Arjen R., Milne, Roger L., Muir, Kenneth R., Newman, William G., Obi, Nadia, Panayiotidis, Mihalis I., Park, Sue K., Park-Simon, Tjoung-Won, Peterlongo, Paolo, Radice, Paolo, Rashid, Muhammad U., Rhenius, Valerie, Saloustros, Emmanouil, Sawyer, Elinor J., Schmidt, Marjanka K., Seibold, Petra, Shah, Mitul, Southey, Melissa C., Teo, Soo Hwang, Tomlinson, Ian, Torres, Diana, Truong, Thérèse, van de Beek, Irma, van der Hout, Annemieke H., Wendt, Camilla C., Dunning, Alison M., Pharoah, Paul D.P., Devilee, Peter, Easton, Douglas F., James, Paul A., and Spurdle, Amanda B.

Published
2024
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38. Branchioma: immunohistochemical and molecular genetic study of 23 cases highlighting frequent loss of retinoblastoma 1 immunoexpression

Author

Bradová, Martina, primary, Thompson, Lester D. R., additional, Hyrcza, Martin, additional, Vaněček, Tomáš, additional, Grossman, Petr, additional, Michal, Michael, additional, Hájková, Veronika, additional, Taheri, Touraj, additional, Rupp, Niels, additional, Suster, David, additional, Lakhani, Sunil, additional, Nikolov, Dimitar Hadži, additional, Žalud, Radim, additional, Skálová, Alena, additional, Michal, Michal, additional, and Agaimy, Abbas, additional

Published
2023
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39. Discrepancies in tumor mutation burden reporting from sequential endobronchial ultrasound transbronchial needle aspiration samples within single lymph node stations - brief report

Author

Fielding, David, primary, Dalley, Andrew J., additional, Singh, Mahendra, additional, Nandakumar, Lakshmy, additional, Lakis, Vanessa, additional, Chittoory, Haarika, additional, Fairbairn, David, additional, Patch, Ann-Marie, additional, Kazakoff, Stephen H., additional, Ferguson, Kaltin, additional, Bashirzadeh, Farzad, additional, Bint, Michael, additional, Pahoff, Carl, additional, Son, Jung Hwa, additional, Ryan, Kimberley, additional, Hodgson, Alan, additional, Sharma, Sowmya, additional, Pearson, John V., additional, Waddell, Nicola, additional, Lakhani, Sunil R., additional, Hartel, Gunter, additional, Simpson, Peter T., additional, and Nones, Katia, additional

Published
2023
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40. Management and 5-year outcomes in 9938 women with screen-detected ductal carcinoma in situ: the UK Sloane Project

Author

Thompson, Alastair, Francis, Adele, Sibbering, Mark, Bishop, Hugh, Carpenter, Robert, George, W.D., Lee, Martin, Nicholson, Stewart, Dobson, Hilary, Evans, Andy, Maxwell, Anthony, Wallis, Matthew, Dodwell, David, Sawyer, Elinor, Adlard, Julian, Dewar, John, Ross, Gillian, Wilcox, Maggie, Hanby, Andrew, Pinder, Sarah, Speirs, Valerie, Thomas, Jeremy, Ellis, Ian, Lakhani, Sunil, Macartney, James, Tomlinson, Ian, Cheung, Shan, Lawrence, Gill, Ball, Graham, Clements, Karen, Hilton, Bridget, Kearins, Olive, Wheaton, Margot, Thompson, Alastair M., Pinder, Sarah E., Ball, Graham R., Thomas, Jeremy St J., Maxwell, Anthony J., Wallis, Matthew G., and Dodwell, David J.

Published
2018
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41. Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group

Author

Amgad, Mohamed, Stovgaard, Elisabeth Specht, Balslev, Eva, Thagaard, Jeppe, Chen, Weijie, Dudgeon, Sarah, Sharma, Ashish, Kerner, Jennifer K., Denkert, Carsten, Yuan, Yinyin, AbdulJabbar, Khalid, Wienert, Stephan, Savas, Peter, Voorwerk, Leonie, Beck, Andrew H., Madabhushi, Anant, Hartman, Johan, Sebastian, Manu M., Horlings, Hugo M., Hudeček, Jan, Ciompi, Francesco, Moore, David A., Singh, Rajendra, Roblin, Elvire, Balancin, Marcelo Luiz, Mathieu, Marie-Christine, Lennerz, Jochen K., Kirtani, Pawan, Chen, I-Chun, Braybrooke, Jeremy P., Pruneri, Giancarlo, Demaria, Sandra, Adams, Sylvia, Schnitt, Stuart J., Lakhani, Sunil R., Rojo, Federico, Comerma, Laura, Badve, Sunil S., Khojasteh, Mehrnoush, Symmans, W. Fraser, Sotiriou, Christos, Gonzalez-Ericsson, Paula, Pogue-Geile, Katherine L., Kim, Rim S., Rimm, David L., Viale, Giuseppe, Hewitt, Stephen M., Bartlett, John M. S., Penault-Llorca, Frédérique, Goel, Shom, Lien, Huang-Chun, Loibl, Sibylle, Kos, Zuzana, Loi, Sherene, Hanna, Matthew G., Michiels, Stefan, Kok, Marleen, Nielsen, Torsten O., Lazar, Alexander J., Bago-Horvath, Zsuzsanna, Kooreman, Loes F. S., van der Laak, Jeroen A. W. M., Saltz, Joel, Gallas, Brandon D., Kurkure, Uday, Barnes, Michael, Salgado, Roberto, and Cooper, Lee A. D.

Published
2020
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42. Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer

Author

Kos, Zuzana, Roblin, Elvire, Kim, Rim S., Michiels, Stefan, Gallas, Brandon D., Chen, Weijie, van de Vijver, Koen K., Goel, Shom, Adams, Sylvia, Demaria, Sandra, Viale, Giuseppe, Nielsen, Torsten O., Badve, Sunil S., Symmans, W. Fraser, Sotiriou, Christos, Rimm, David L., Hewitt, Stephen, Denkert, Carsten, Loibl, Sibylle, Luen, Stephen J., Bartlett, John M. S., Savas, Peter, Pruneri, Giancarlo, Dillon, Deborah A., Cheang, Maggie Chon U., Tutt, Andrew, Hall, Jacqueline A., Kok, Marleen, Horlings, Hugo M., Madabhushi, Anant, van der Laak, Jeroen, Ciompi, Francesco, Laenkholm, Anne-Vibeke, Bellolio, Enrique, Gruosso, Tina, Fox, Stephen B., Araya, Juan Carlos, Floris, Giuseppe, Hudeček, Jan, Voorwerk, Leonie, Beck, Andrew H., Kerner, Jen, Larsimont, Denis, Declercq, Sabine, Van den Eynden, Gert, Pusztai, Lajos, Ehinger, Anna, Yang, Wentao, AbdulJabbar, Khalid, Yuan, Yinyin, Singh, Rajendra, Hiley, Crispin, Bakir, Maise al, Lazar, Alexander J., Naber, Stephen, Wienert, Stephan, Castillo, Miluska, Curigliano, Giuseppe, Dieci, Maria-Vittoria, André, Fabrice, Swanton, Charles, Reis-Filho, Jorge, Sparano, Joseph, Balslev, Eva, Chen, I-Chun, Stovgaard, Elisabeth Ida Specht, Pogue-Geile, Katherine, Blenman, Kim R. M., Penault-Llorca, Frédérique, Schnitt, Stuart, Lakhani, Sunil R., Vincent-Salomon, Anne, Rojo, Federico, Braybrooke, Jeremy P., Hanna, Matthew G., Soler-Monsó, M. Teresa, Bethmann, Daniel, Castaneda, Carlos A., Willard-Gallo, Karen, Sharma, Ashish, Lien, Huang-Chun, Fineberg, Susan, Thagaard, Jeppe, Comerma, Laura, Gonzalez-Ericsson, Paula, Brogi, Edi, Loi, Sherene, Saltz, Joel, Klaushen, Frederick, Cooper, Lee, Amgad, Mohamed, Moore, David A., and Salgado, Roberto

Published
2020
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44. Improved concordance of challenging human epidermal growth factor receptor 2 dual in‐situ hybridisation cases with the use of a digital image analysis algorithm in breast cancer

Author

Gough, Madeline, primary, Liu, Cheng, additional, Srinivasan, Bhuvana, additional, Wilkinson, Lisa, additional, Dunk, Louisa, additional, Yang, Yuanhao, additional, Schreiber, Veronika, additional, Tuffaha, Haitham, additional, Kryza, Thomas, additional, Hooper, John D, additional, Lakhani, Sunil R, additional, and Snell, Cameron E, additional

Published
2023
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47. Breast ductal carcinoma in situ carry mutational driver events representative of invasive breast cancer

Author

Pang, Jia-Min B, Savas, Peter, Fellowes, Andrew P, Mir Arnau, Gisela, Kader, Tanjina, Vedururu, Ravikiran, Hewitt, Chelsee, Takano, Elena A, Byrne, David J, Choong, David YH, Millar, Ewan KA, Lee, C Soon, O'Toole, Sandra A, Lakhani, Sunil R, Cummings, Margaret C, Mann, G Bruce, Campbell, Ian G, Dobrovic, Alexander, Loi, Sherene, Gorringe, Kylie L, and Fox, Stephen B

Published
2017
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48. Proteogenomic analysis of Inhibitor of Differentiation 4 (ID4) in basal-like breast cancer

Author

Baker, Laura A., Holliday, Holly, Roden, Daniel, Krisp, Christoph, Wu, Sunny Z., Junankar, Simon, Serandour, Aurelien A., Mohammed, Hisham, Nair, Radhika, Sankaranarayanan, Geetha, Law, Andrew M. K., McFarland, Andrea, Simpson, Peter T., Lakhani, Sunil, Dodson, Eoin, Selinger, Christina, Anderson, Lyndal, Samimi, Goli, Hacker, Neville F., Lim, Elgene, Ormandy, Christopher J., Naylor, Matthew J., Simpson, Kaylene, Nikolic, Iva, O’Toole, Sandra, Kaplan, Warren, Cowley, Mark J., Carroll, Jason S., Molloy, Mark, and Swarbrick, Alexander

Published
2020
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49. Non-coding RNAs underlie genetic predisposition to breast cancer

Author

Moradi Marjaneh, Mahdi, Beesley, Jonathan, O’Mara, Tracy A., Mukhopadhyay, Pamela, Koufariotis, Lambros T., Kazakoff, Stephen, Hussein, Nehal, Fachal, Laura, Bartonicek, Nenad, Hillman, Kristine M., Kaufmann, Susanne, Sivakumaran, Haran, Smart, Chanel E., McCart Reed, Amy E., Ferguson, Kaltin, Saunus, Jodi M., Lakhani, Sunil R., Barnes, Daniel R., Antoniou, Antonis C., Dinger, Marcel E., Waddell, Nicola, Easton, Douglas F., Dunning, Alison M., Chenevix-Trench, Georgia, Edwards, Stacey L., and French, Juliet D.

Published
2020
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50. Differential response of placental cells to high D‐glucose and its impact on extracellular vesicle biogenesis and trafficking via small GTPase Ras‐related protein RAB‐7A.

Author

Palma, Carlos, Lai, Andrew, Scholz‐Romero, Katherin, Chittoory, Haarika, Van Haeringen, Benjamin, Carrion, Flavio, Handberg, Aase, Lappas, Martha, Lakhani, Sunil R, McCart Reed, Amy E, McIntyre, H. David, Nair, Soumyalekshmi, and Salomon, Carlos

Subjects
EXTRACELLULAR vesicles, HEAT shock proteins, PREGNANCY proteins, GESTATIONAL diabetes, PLACENTA, PLACENTAL growth factor, GUANOSINE triphosphatase
Abstract

Placental extracellular vesicles (EVs) can be found in the maternal circulation throughout gestation, and their concentration, content and bioactivity are associated with pregnancy outcomes, including gestational diabetes mellitus (GDM). However, the effect of changes in the maternal microenvironment on the mechanisms associated with the secretion of EVs from placental cells remains to be fully established. Here, we evaluated the effect of high glucose on proteins associated with the trafficking and release of different populations of EVs from placental cells. BeWo and HTR8/SVneo cells were used as placental models and cultured under 5‐mM D‐glucose (i.e. control) or 25‐mM D‐glucose (high glucose). Cell‐conditioned media (CCM) and cell lysate were collected after 48 h. Different populations of EVs were isolated from CCM by ultracentrifugation (i.e. pellet 2K‐g, pellet 10K‐g, and pellet 100K‐g) and characterised by Nanoparticle Tracking Analysis. Quantitative proteomic analysis (IDA/SWATH) and multiple reaction monitoring protocols at high resolution (MRMHR) were developed to quantify 37 proteins related to biogenesis, trafficking/release and recognition/uptake of EVs. High glucose increased the secretion of total EVs across the pellets from BeWo cells, an effect driven mainly by changes in the small EVs concentration in the CCM. Interestingly, no effect of high glucose on HTR8/SVneo cells EVs secretion was observed. High glucose induces changes in proteins associated with vesicle trafficking in BeWo cells, including Heat Shock Protein Family A (Hsp70) Member 9 (HSPA9) and Member 8 (HSPA8). For HTR8/SVneo, altered proteins including prostaglandin F2α receptor regulatory protein (FPRP), RAB5A, RAB35, RAB5B, and RB11B, STAM1 and TSG101. These proteins are associated with the secretion and trafficking of EVs, which could explain in part, changes in the levels of circulating EVs in diabetic pregnancies. Further, we identified that proteins RAB11B, PDCD6IP, STAM, HSPA9, HSPA8, SDCBP, RAB5B, RAB5A, RAB7A and ERAP1 regulate EV release in response to high and low glucose when overexpressed in cells. Interestingly, immunohistochemistry analysis of RAB7A revealed distinct changes in placental tissues obtained from women with normal glucose tolerance (NGT, n = 6) and those with GDM (n = 6), influenced by diet or insulin treatment. High glucose regulation of proteins involved in intercellular dynamics and the trafficking of multivesicular bodies to the plasma membrane in placental cells is relevant in the context of GDM pregnancies. [ABSTRACT FROM AUTHOR]

Published
2024
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