Search

Your search keyword '"Bowtell, D.D."' showing total 13 results
Start Over Author "Bowtell, D.D."
13 results on '"Bowtell, D.D."'

1. Prognostic gene expression signature for high-grade serous ovarian cancer

Author

Bowtell, D., Chenevix-Trench, G., Green, A., Webb, P., DeFazio, A., Gertig, D., Traficante, N., Fereday, S., Moore, S., Hung, J., Harrap, K., Sadkowsky, T., Pandeya, N., Malt, M., Mellon, A., Robertson, R., Vanden Bergh, T., Jones, M., Mackenzie, P., Maidens, J., Nattress, K., Chiew, Y.E., Stenlake, A., Sullivan, H., Alexander, B., Ashover, P., Brown, S., Corrish, T., Green, L., Jackman, L., Ferguson, K., Martin, K., Martyn, A., Ranieri, B., White, J., Jayde, V., Mamers, P., Bowes, L., Galletta, L., Giles, D., Hendley, J., Alsop, K., Schmidt, T., Shirley, H., Ball, C., Young, C., Viduka, S., Tran, Hoa, Bilic, Sanela, Glavinas, Lydia, Brooks, Julia, Stuart-Harris, R., Kirsten, F., Rutovitz, J., Clingan, P., Glasgow, A., Proietto, A., Braye, S., Otton, G., Shannon, J., Bonaventura, T., Stewart, J., Begbie, S., Friedlander, M., Bell, D., Baron-Hay, S., Ferrier,a, A., Gard, G., Nevell, D., Pavlakis, N., Valmadre, S., Young, B., Camaris, C., Crouch, R., Edwards, L., Hacker, N., Marsden, D., Robertson, G., Beale, P., Beith, J., Carter, J., Dalrymple, C., Houghton, R., Russell, P., Links, M., Grygiel, J., Hill, J., Brand, A., Byth, K., Jaworski, R., Harnett, P., Sharma, R., Wain, G., Ward, B., Papadimos, D., Crandon, A., Cummings, M., Horwood, K., Obermair, A., Perrin, L., Wyld, D., Nicklin, J., Davy, M., Oehler, M.K., Hall, C., Dodd, T., Healy, T., Pittman, K., Henderson, D., Miller, J., Pierdes, J., Blomfield, P., Challis, D., McIntosh, R., Parker, A., Brown, B., Rome, R., Allen, D., Grant, P., Hyde, S., Laurie, R., Robbie, M., Healy, D., Jobling, T., Manolitsas, T., McNealage, J., Rogers, P., Susil, B., Sumithran, E., Simpson, I., Phillips, K., Rischin, D., Fox, S., Johnson, D., Lade, S., Loughrey, M., O’Callaghan, N., Murray, W., Waring, P., Billson, V., Pyman, J., Neesham, D., Quinn, M., Underhill, C., Bell, R., Ng, L.F., Blum, R., Ganju, V., Hammond, I., Leung, Y., McCartney, A., Buck, M., Haviv, I., Purdie, D., Whiteman, D., Zeps, N., Millstein, J., Budden, T., Goode, E.L., Anglesio, M.S., Talhouk, A., Intermaggio, M.P., Leong, H.S., Chen, S., Elatre, W., Gilks, B., Nazeran, T., Volchek, M., Bentley, R.C., Wang, C., Chiu, D.S., Kommoss, S., Leung, S.C.Y., Senz, J., Lum, A., Chow, V., Sudderuddin, H., Mackenzie, R., George, J., Steed, H., Koziak, J.M., Köbel, M., McNeish, I.A., Goranova, T., Ennis, D., Macintyre, G., Silva De Silva, D., Ramón y Cajal, T., García-Donas, J., Hernando Polo, S., Rodriguez, G.C., Cushing-Haugen, K.L., Harris, H.R., Greene, C.S., Zelaya, R.A., Behrens, S., Fortner, R.T., Sinn, P., Herpel, E., Lester, J., Lubiński, J., Oszurek, O., Tołoczko, A., Cybulski, C., Menkiszak, J., Pearce, C.L., Pike, M.C., Tseng, C., Alsop, J., Rhenius, V., Song, H., Jimenez-Linan, M., Piskorz, A.M., Gentry-Maharaj, A., Karpinskyj, C., Widschwendter, M., Singh, N., Kennedy, C.J., Harnett, P.R., Gao, B., Johnatty, S.E., Sayer, R., Boros, J., Winham, S.J., Keeney, G.L., Kaufmann, S.H., Larson, M.C., Luk, H., Hernandez, B.Y., Thompson, P.J., Wilkens, L.R., Carney, M.E., Trabert, B., Lissowska, J., Brinton, L., Sherman, M.E., Bodelon, C., Hinsley, S., Lewsley, L.A., Glasspool, R., Banerjee, S.N., Stronach, E.A., Haluska, P., Ray-Coquard, I., Mahner, S., Winterhoff, B., Slamon, D., Levine, D.A., Kelemen, L.E., Benitez, J., Chang-Claude, J., Gronwald, J., Wu, A.H., Menon, U., Goodman, M.T., Schildkraut, J.M., Wentzensen, N., Brown, R., Berchuck, A., deFazio, A., Gayther, S.A., García, M.J., Henderson, M.J., Rossing, M.A., Beeghly-Fadiel, A., Fasching, P.A., Orsulic, S., Karlan, B.Y., Konecny, G.E., Huntsman, D.G., Bowtell, D.D., Brenton, J.D., Doherty, J.A., Pharoah, P.D.P., and Ramus, S.J.

Published
2020
Full Text
View/download PDF

2. The evolutionary history of 2,658 cancers

Author

Gerstung, M., Jolly, C., Leshchiner, I., Dentro, S.C., Gonzalez, S., Rosebrock, D., Mitchell, T.J., Rubanova, Y., Anur, P., Yu, K., Tarabichi, M., Deshwar, A.G., Wintersinger, J., Kleinheinz, K., Vázquez-García, I., Haase, K., Jerman, L., Sengupta, Subhajit, Macintyre, G., Malikic, S., Donmez, N., Livitz, D.G., Cmero, M., Demeulemeester, J., Schumacher, S., Fan, Y., Yao, X., Lee, J., Schlesner, M., Boutros, P.C., Bowtell, D.D., Zhu, H., Getz, G., Imielinski, M., Beroukhim, R., Sahinalp, S.C., Ji, Y., Peifer, M., Markowetz, F., Mustonen, V., Yuan, K., Wang, W., Morris, Q.D., Adams, D.J., Campbell, P.J., Cao, S., Christie, E.L., Cun, Y., Dawson, K.J., Drews, R.M., Eils, R., Fittall, M., Garsed, D.W., Ha, G., Lee-Six, H., Martincorena, I., Oesper, L., Peto, M., Raphael, B.J., Salcedo, A., Sengupta, S., Shi, R., Shin, S.J., Spiro, O., Stein, L.D., Vembu, S., Wheeler, D.A., Yang, T.-P., Spellman, P.T., Wedge, D.C., Van Loo, P., Apollo - University of Cambridge Repository, Organismal and Evolutionary Biology Research Programme, Helsinki Institute for Information Technology, Institute of Biotechnology, Bioinformatics, Department of Computer Science, Doctoral Programme in Computer Science, and Markowetz, Florian [0000-0002-2784-5308]

Subjects
Genome instability, SELECTION, DNA Repair, Gene Dosage, PROGRESSION, medicine.disease_cause, Somatic evolution in cancer, Genome, 0302 clinical medicine, Neoplasms, MUTATIONAL PROCESSES, Cancer genomics, 2.1 Biological and endogenous factors, Genes, Tumor Suppressor, Aetiology, Cancer, Genetics, 0303 health sciences, Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], Multidisciplinary, Manchester Cancer Research Centre, WOMEN, Neoplasms/genetics, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], 3. Good health, 030220 oncology & carcinogenesis, SEX, Tumor Suppressor, Human, SOMATIC MUTATION, BRANCHED EVOLUTION, Evolution, General Science & Technology, Isochromosome, 3122 Cancers, Computational biology, Biology, BREAST, Article, Evolution, Molecular, 03 medical and health sciences, DNA Repair/genetics, Germline mutation, Rare Diseases, Molecular evolution, Insertional, medicine, Humans, ddc:610, PCAWG Evolution & Heterogeneity Working Group, Gene, 030304 developmental biology, LANDSCAPE, Genome, Human, ResearchInstitutes_Networks_Beacons/mcrc, Point mutation, Human Genome, PCAWG Consortium, Molecular, Genetic Variation, NATURAL-HISTORY, medicine.disease, Human genetics, Computational biology and bioinformatics, Brain Disorders, Brain Cancer, Mutagenesis, Insertional, Genes, Mutagenesis, Genome, Human/genetics, Human genome, Carcinogenesis, Mutagenesis, Insertional/genetics
Abstract

Cancer develops through a process of somatic evolution1,2. Sequencing data from a single biopsy represent a snapshot of this process that can reveal the timing of specific genomic aberrations and the changing influence of mutational processes3. Here, by whole-genome sequencing analysis of 2,658 cancers as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)4, we reconstruct the life history and evolution of mutational processes and driver mutation sequences of 38 types of cancer. Early oncogenesis is characterized by mutations in a constrained set of driver genes, and specific copy number gains, such as trisomy 7 in glioblastoma and isochromosome 17q in medulloblastoma. The mutational spectrum changes significantly throughout tumour evolution in 40% of samples. A nearly fourfold diversification of driver genes and increased genomic instability are features of later stages. Copy number alterations often occur in mitotic crises, and lead to simultaneous gains of chromosomal segments. Timing analyses suggest that driver mutations often precede diagnosis by many years, if not decades. Together, these results determine the evolutionary trajectories of cancer, and highlight opportunities for early cancer detection., Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

Published
2020

3. Reconstructing evolutionary trajectories of mutation signature activities in cancer using TrackSig

Author

Rubanova, Y., Shi, R., Harrigan, C.F., Li, R., Wintersinger, J., Sahin, N., Deshwar, A.G., Dentro, S.C., Leshchiner, I., Gerstung, M., Jolly, C., Haase, K., Tarabichi, M., Yu, K., Gonzalez, S., Macintyre, G., Adams, D.J., Anur, P., Beroukhim, R., Boutros, P.C., Bowtell, D.D., Campbell, P.J., Cao, S., Christie, E.L., Cmero, M., Cun, Y., Dawson, K.J., Demeulemeester, J., Donmez, N., Drews, R.M., Eils, R., Fan, Y., Fittall, M., Garsed, D.W., Getz, G., Ha, G., Imielinski, M., Jerman, L., Ji, Y., Kleinheinz, K., Lee, J., Lee-Six, H., Livitz, D.G., Malikic, S., Markowetz, F., Martincorena, I., Mitchell, T.J., Mustonen, V., Oesper, L., Peifer, M., Peto, M., Raphael, B.J., Rosebrock, D., Sahinalp, S.C., Salcedo, A., Schlesner, M., Schumacher, S., Sengupta, Subhajit, Shin, S.J., Spiro, O., Stein, L.D., Vázquez-García, I., Vembu, S., Wheeler, D.A., Yang, T.-P., Yao, X., Yuan, K., Zhu, H., Wang, W., Morris, Q., Spellman, P.T., Wedge, D.C., Van Loo, P., Harrigan, Caitlin F [0000-0002-9243-9648], Morris, Quaid D [0000-0002-2760-6999], Apollo - University of Cambridge Repository, Organismal and Evolutionary Biology Research Programme, Helsinki Institute for Information Technology, Institute of Biotechnology, Bioinformatics, Department of Computer Science, Wedge, DC, and Dentro, SC

Subjects
0301 basic medicine, Medizin, General Physics and Astronomy, Genome, 0302 clinical medicine, Gene Frequency, Ecology,Evolution & Ethology, Neoplasms, 2.1 Biological and endogenous factors, Computational models, Aetiology, lcsh:Science, Cancer genetics, Cancer, Human Biology & Physiology, Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], Multidisciplinary, Manchester Cancer Research Centre, 1184 Genetics, developmental biology, physiology, Single Nucleotide, Neoplasms/genetics, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], 3. Good health, 030220 oncology & carcinogenesis, Mutation (genetic algorithm), 1181 Ecology, evolutionary biology, Genetics & Genomics, Human, Neutral mutation, Evolution, Science, Context (language use), Computational biology, Biology, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, Article, Evolution, Molecular, 03 medical and health sciences, Rare Diseases, Genetics, medicine, PCAWG Evolution and Heterogeneity Working Group, Humans, Computer Simulation, ddc:610, Polymorphism, Allele frequency, Computational & Systems Biology, Whole genome sequencing, Whole Genome Sequencing, Genome, Human, ResearchInstitutes_Networks_Beacons/mcrc, Human Genome, Molecular, Computational Biology, PCAWG Consortium, General Chemistry, Computational Biology/methods, Tumour Biology, medicine.disease, 113 Computer and information sciences, 030104 developmental biology, Mutation, Human genome, lcsh:Q
Abstract

The type and genomic context of cancer mutations depend on their causes. These causes have been characterized using signatures that represent mutation types that co-occur in the same tumours. However, it remains unclear how mutation processes change during cancer evolution due to the lack of reliable methods to reconstruct evolutionary trajectories of mutational signature activity. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole-genome sequencing data from 2658 cancers across 38 tumour types, we present TrackSig, a new method that reconstructs these trajectories using optimal, joint segmentation and deconvolution of mutation type and allele frequencies from a single tumour sample. In simulations, we find TrackSig has a 3–5% activity reconstruction error, and 12% false detection rate. It outperforms an aggressive baseline in situations with branching evolution, CNA gain, and neutral mutations. Applied to data from 2658 tumours and 38 cancer types, TrackSig permits pan-cancer insight into evolutionary changes in mutational processes., Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

Published
2020
Full Text
View/download PDF

4. Prognostic gene expression signature for high-grade serous ovarian cancer

Author

Millstein, J., primary, Budden, T., additional, Goode, E.L., additional, Anglesio, M.S., additional, Talhouk, A., additional, Intermaggio, M.P., additional, Leong, H.S., additional, Chen, S., additional, Elatre, W., additional, Gilks, B., additional, Nazeran, T., additional, Volchek, M., additional, Bentley, R.C., additional, Wang, C., additional, Chiu, D.S., additional, Kommoss, S., additional, Leung, S.C.Y., additional, Senz, J., additional, Lum, A., additional, Chow, V., additional, Sudderuddin, H., additional, Mackenzie, R., additional, George, J., additional, Fereday, S., additional, Hendley, J., additional, Traficante, N., additional, Steed, H., additional, Koziak, J.M., additional, Köbel, M., additional, McNeish, I.A., additional, Goranova, T., additional, Ennis, D., additional, Macintyre, G., additional, Silva De Silva, D., additional, Ramón y Cajal, T., additional, García-Donas, J., additional, Hernando Polo, S., additional, Rodriguez, G.C., additional, Cushing-Haugen, K.L., additional, Harris, H.R., additional, Greene, C.S., additional, Zelaya, R.A., additional, Behrens, S., additional, Fortner, R.T., additional, Sinn, P., additional, Herpel, E., additional, Lester, J., additional, Lubiński, J., additional, Oszurek, O., additional, Tołoczko, A., additional, Cybulski, C., additional, Menkiszak, J., additional, Pearce, C.L., additional, Pike, M.C., additional, Tseng, C., additional, Alsop, J., additional, Rhenius, V., additional, Song, H., additional, Jimenez-Linan, M., additional, Piskorz, A.M., additional, Gentry-Maharaj, A., additional, Karpinskyj, C., additional, Widschwendter, M., additional, Singh, N., additional, Kennedy, C.J., additional, Sharma, R., additional, Harnett, P.R., additional, Gao, B., additional, Johnatty, S.E., additional, Sayer, R., additional, Boros, J., additional, Winham, S.J., additional, Keeney, G.L., additional, Kaufmann, S.H., additional, Larson, M.C., additional, Luk, H., additional, Hernandez, B.Y., additional, Thompson, P.J., additional, Wilkens, L.R., additional, Carney, M.E., additional, Trabert, B., additional, Lissowska, J., additional, Brinton, L., additional, Sherman, M.E., additional, Bodelon, C., additional, Hinsley, S., additional, Lewsley, L.A., additional, Glasspool, R., additional, Banerjee, S.N., additional, Stronach, E.A., additional, Haluska, P., additional, Ray-Coquard, I., additional, Mahner, S., additional, Winterhoff, B., additional, Slamon, D., additional, Levine, D.A., additional, Kelemen, L.E., additional, Benitez, J., additional, Chang-Claude, J., additional, Gronwald, J., additional, Wu, A.H., additional, Menon, U., additional, Goodman, M.T., additional, Schildkraut, J.M., additional, Wentzensen, N., additional, Brown, R., additional, Berchuck, A., additional, Chenevix-Trench, G., additional, deFazio, A., additional, Gayther, S.A., additional, García, M.J., additional, Henderson, M.J., additional, Rossing, M.A., additional, Beeghly-Fadiel, A., additional, Fasching, P.A., additional, Orsulic, S., additional, Karlan, B.Y., additional, Konecny, G.E., additional, Huntsman, D.G., additional, Bowtell, D.D., additional, Brenton, J.D., additional, Doherty, J.A., additional, Pharoah, P.D.P., additional, Ramus, S.J., additional, Bowtell, D., additional, Green, A., additional, Webb, P., additional, DeFazio, A., additional, Gertig, D., additional, Moore, S., additional, Hung, J., additional, Harrap, K., additional, Sadkowsky, T., additional, Pandeya, N., additional, Malt, M., additional, Mellon, A., additional, Robertson, R., additional, Vanden Bergh, T., additional, Jones, M., additional, Mackenzie, P., additional, Maidens, J., additional, Nattress, K., additional, Chiew, Y.E., additional, Stenlake, A., additional, Sullivan, H., additional, Alexander, B., additional, Ashover, P., additional, Brown, S., additional, Corrish, T., additional, Green, L., additional, Jackman, L., additional, Ferguson, K., additional, Martin, K., additional, Martyn, A., additional, Ranieri, B., additional, White, J., additional, Jayde, V., additional, Mamers, P., additional, Bowes, L., additional, Galletta, L., additional, Giles, D., additional, Alsop, K., additional, Schmidt, T., additional, Shirley, H., additional, Ball, C., additional, Young, C., additional, Viduka, S., additional, Tran, Hoa, additional, Bilic, Sanela, additional, Glavinas, Lydia, additional, Brooks, Julia, additional, Stuart-Harris, R., additional, Kirsten, F., additional, Rutovitz, J., additional, Clingan, P., additional, Glasgow, A., additional, Proietto, A., additional, Braye, S., additional, Otton, G., additional, Shannon, J., additional, Bonaventura, T., additional, Stewart, J., additional, Begbie, S., additional, Friedlander, M., additional, Bell, D., additional, Baron-Hay, S., additional, Ferrier,a, A., additional, Gard, G., additional, Nevell, D., additional, Pavlakis, N., additional, Valmadre, S., additional, Young, B., additional, Camaris, C., additional, Crouch, R., additional, Edwards, L., additional, Hacker, N., additional, Marsden, D., additional, Robertson, G., additional, Beale, P., additional, Beith, J., additional, Carter, J., additional, Dalrymple, C., additional, Houghton, R., additional, Russell, P., additional, Links, M., additional, Grygiel, J., additional, Hill, J., additional, Brand, A., additional, Byth, K., additional, Jaworski, R., additional, Harnett, P., additional, Wain, G., additional, Ward, B., additional, Papadimos, D., additional, Crandon, A., additional, Cummings, M., additional, Horwood, K., additional, Obermair, A., additional, Perrin, L., additional, Wyld, D., additional, Nicklin, J., additional, Davy, M., additional, Oehler, M.K., additional, Hall, C., additional, Dodd, T., additional, Healy, T., additional, Pittman, K., additional, Henderson, D., additional, Miller, J., additional, Pierdes, J., additional, Blomfield, P., additional, Challis, D., additional, McIntosh, R., additional, Parker, A., additional, Brown, B., additional, Rome, R., additional, Allen, D., additional, Grant, P., additional, Hyde, S., additional, Laurie, R., additional, Robbie, M., additional, Healy, D., additional, Jobling, T., additional, Manolitsas, T., additional, McNealage, J., additional, Rogers, P., additional, Susil, B., additional, Sumithran, E., additional, Simpson, I., additional, Phillips, K., additional, Rischin, D., additional, Fox, S., additional, Johnson, D., additional, Lade, S., additional, Loughrey, M., additional, O’Callaghan, N., additional, Murray, W., additional, Waring, P., additional, Billson, V., additional, Pyman, J., additional, Neesham, D., additional, Quinn, M., additional, Underhill, C., additional, Bell, R., additional, Ng, L.F., additional, Blum, R., additional, Ganju, V., additional, Hammond, I., additional, Leung, Y., additional, McCartney, A., additional, Buck, M., additional, Haviv, I., additional, Purdie, D., additional, Whiteman, D., additional, and Zeps, N., additional

Published
2020
Full Text
View/download PDF

5. Methylation of all BRCA1 copies predicts response to the PARP inhibitor rucaparib in ovarian carcinoma.

Author

Jones M., Ferguson K., Martin K., Martyn A., Ranieri B., White J., Jayde V., Mamers P., Bowes L., Giles D., Hendley J., Schmidt T., Shirley H., Ball C., Young C., Viduka S., Tran H., Bilic S., Glavinas L., Brooks J., Stuart-Harris R., Kirsten F., Rutovitz J., Brand A., Byth K., Jaworski R., Harnett P., Sharma R., Wain G., Ward B., Papadimos D., Crandon A., Cummings M., Horwood K., Obermair A., Perrin L., Wyld D., Nicklin J., Davy M., Oehler M.K., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Hyde S., Laurie R., Robbie M., Healy D., Manolitsas T., McNealage J., Rogers P., Susil B., Sumithran E., Simpson I., Phillips K., Rischin D., Fox S., Johnson D., Lade S., Loughrey M., O'Callaghan N., Murray W., Waring P., Billson V., Pyman J., Neesham D., Quinn M., Underhill C., Ng L.F., Blum R., Ganju V., Hammond I., Leung Y., McCartney A., Buck M., Haviv I., Purdie D., Whiteman D., Zeps N., deFazio A., McNeish I.A., Bowtell D.D., Swisher E.M., Dobrovic A., Wakefield M.J., Scott C.L., Bell R., Jobling T., Kondrashova O., Topp M., Nesic K., Lieschke E., Ho G.-Y., Harrell M.I., Zapparoli G.V., Hadley A., Holian R., Boehm E., Heong V., Sanij E., Pearson R.B., Krais J.J., Johnson N., McNally O., Ananda S., Alsop K., Hutt K.J., Kaufmann S.H., Lin K.K., Harding T.C., Traficante N., Chenevix-Trench G., Green A., Webb P., Gertig D., Fereday S., Moore S., Hung J., Harrap K., Sadkowsky T., Pandeya N., Malt M., Mellon A., Robertson R., VandenBergh T., Mackenzie P., Maidens J., Nattress K., Chiew Y.E., Stenlake A., Sullivan H., Alexander B., Ashover P., Brown S., Corrish T., Green L., Jackman L., Galletta L., Clingan P., Glasgow A., Proietto A., Braye S., Otton G., Shannon J., Bonaventura T., Stewart J., Begbie S., Friedlander M., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Pavlakis N., Valmadre S., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Houghton R., Russell P., Links M., Grygiel J., Hill J., Jones M., Ferguson K., Martin K., Martyn A., Ranieri B., White J., Jayde V., Mamers P., Bowes L., Giles D., Hendley J., Schmidt T., Shirley H., Ball C., Young C., Viduka S., Tran H., Bilic S., Glavinas L., Brooks J., Stuart-Harris R., Kirsten F., Rutovitz J., Brand A., Byth K., Jaworski R., Harnett P., Sharma R., Wain G., Ward B., Papadimos D., Crandon A., Cummings M., Horwood K., Obermair A., Perrin L., Wyld D., Nicklin J., Davy M., Oehler M.K., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Hyde S., Laurie R., Robbie M., Healy D., Manolitsas T., McNealage J., Rogers P., Susil B., Sumithran E., Simpson I., Phillips K., Rischin D., Fox S., Johnson D., Lade S., Loughrey M., O'Callaghan N., Murray W., Waring P., Billson V., Pyman J., Neesham D., Quinn M., Underhill C., Ng L.F., Blum R., Ganju V., Hammond I., Leung Y., McCartney A., Buck M., Haviv I., Purdie D., Whiteman D., Zeps N., deFazio A., McNeish I.A., Bowtell D.D., Swisher E.M., Dobrovic A., Wakefield M.J., Scott C.L., Bell R., Jobling T., Kondrashova O., Topp M., Nesic K., Lieschke E., Ho G.-Y., Harrell M.I., Zapparoli G.V., Hadley A., Holian R., Boehm E., Heong V., Sanij E., Pearson R.B., Krais J.J., Johnson N., McNally O., Ananda S., Alsop K., Hutt K.J., Kaufmann S.H., Lin K.K., Harding T.C., Traficante N., Chenevix-Trench G., Green A., Webb P., Gertig D., Fereday S., Moore S., Hung J., Harrap K., Sadkowsky T., Pandeya N., Malt M., Mellon A., Robertson R., VandenBergh T., Mackenzie P., Maidens J., Nattress K., Chiew Y.E., Stenlake A., Sullivan H., Alexander B., Ashover P., Brown S., Corrish T., Green L., Jackman L., Galletta L., Clingan P., Glasgow A., Proietto A., Braye S., Otton G., Shannon J., Bonaventura T., Stewart J., Begbie S., Friedlander M., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Pavlakis N., Valmadre S., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Houghton R., Russell P., Links M., Grygiel J., and Hill J.

Abstract

Accurately identifying patients with high-grade serous ovarian carcinoma (HGSOC) who respond to poly(ADP-ribose) polymerase inhibitor (PARPi) therapy is of great clinical importance. Here we show that quantitative BRCA1 methylation analysis provides new insight into PARPi response in preclinical models and ovarian cancer patients. The response of 12 HGSOC patient-derived xenografts (PDX) to the PARPi rucaparib was assessed, with variable dose-dependent responses observed in chemo-naive BRCA1/2-mutated PDX, and no responses in PDX lacking DNA repair pathway defects. Among BRCA1-methylated PDX, silencing of all BRCA1 copies predicts rucaparib response, whilst heterozygous methylation is associated with resistance. Analysis of 21 BRCA1-methylated platinum-sensitive recurrent HGSOC (ARIEL2 Part 1 trial) confirmed that homozygous or hemizygous BRCA1 methylation predicts rucaparib clinical response, and that methylation loss can occur after exposure to chemotherapy. Accordingly, quantitative BRCA1 methylation analysis in a pre-treatment biopsy could allow identification of patients most likely to benefit, and facilitate tailoring of PARPi therapy.Copyright © 2018, The Author(s).

Published
2018

6. Traceback: A Proposed Framework to Increase Identification and Genetic Counseling of BRCA1 and BRCA2 Mutation Carriers Through Family-Based Outreach

Author

Samimi, G., Bernardini, M.Q., Brody, L.C., Caga-Anan, C.F., Campbell, I.G., Chenevix-Trench, G., Couch, F.J., Dean, M., Hullu, J.A. de, Domchek, S.M., Drapkin, R., Spencer Feigelson, H., Friedlander, M., Gaudet, M.M., Harmsen, M.G., Hurley, K., James, P.A., Kwon, J.S., Lacbawan, F., Lheureux, S., Mai, P.L., Mechanic, L.E., Minasian, L.M., Myers, E.R., Robson, M.E., Ramus, S.J., Rezende, L.F., Shaw, P.A., Slavin, T.P., Swisher, E.M., Takenaka, M., Bowtell, D.D., Sherman, M.E., Samimi, G., Bernardini, M.Q., Brody, L.C., Caga-Anan, C.F., Campbell, I.G., Chenevix-Trench, G., Couch, F.J., Dean, M., Hullu, J.A. de, Domchek, S.M., Drapkin, R., Spencer Feigelson, H., Friedlander, M., Gaudet, M.M., Harmsen, M.G., Hurley, K., James, P.A., Kwon, J.S., Lacbawan, F., Lheureux, S., Mai, P.L., Mechanic, L.E., Minasian, L.M., Myers, E.R., Robson, M.E., Ramus, S.J., Rezende, L.F., Shaw, P.A., Slavin, T.P., Swisher, E.M., Takenaka, M., Bowtell, D.D., and Sherman, M.E.

Abstract

Item does not contain fulltext, In May 2016, the Division of Cancer Prevention and the Division of Cancer Control and Population Sciences, National Cancer Institute, convened a workshop to discuss a conceptual framework for identifying and genetically testing previously diagnosed but unreferred patients with ovarian cancer and other unrecognized BRCA1 or BRCA2 mutation carriers to improve the detection of families at risk for breast or ovarian cancer. The concept, designated Traceback, was prompted by the recognition that although BRCA1 and BRCA2 mutations are frequent in women with ovarian cancer, many such women have not been tested, especially if their diagnosis predated changes in testing guidelines. The failure to identify mutation carriers among probands represents a lost opportunity to prevent cancer in unsuspecting relatives through risk-reduction intervention in mutation carriers and to provide appropriate reassurances to noncarriers. The Traceback program could provide an important opportunity to reach families from racial, ethnic, and socioeconomic groups who historically have not sought or been offered genetic counseling and testing and thereby contribute to a reduction in health disparities in women with germline BRCA mutations. To achieve an interdisciplinary perspective, the workshop assembled international experts in genetics, medical and gynecologic oncology, clinical psychology, epidemiology, genomics, cost-effectiveness modeling, pathology, bioethics, and patient advocacy to identify factors to consider when undertaking a Traceback program. This report highlights the workshop deliberations with the goal of stimulating research and providing a framework for pilot studies to assess the feasibility and ethical and logistical considerations related to the development of best practices for implementation of Traceback studies.

Published
2017

8. Role of molecular agents and targeted therapy in clinical trials for women with ovarian cancer

Author

Ledermann, J.A., Marth, C., Carey, M.S., Birrer, M., Bowtell, D.D., Kaye, S., McNeish, I., Oza, A., Scambia, G., Rustin, G., Stehman, F.B., Gershenson, D., Thomas, G., Berns, E., Casado, A., Ottevanger, N., Hilpert, F., Kim, B.G., Okamoto, A., Bacon, M., Kitchener, H., Stuart, G.C., Ledermann, J.A., Marth, C., Carey, M.S., Birrer, M., Bowtell, D.D., Kaye, S., McNeish, I., Oza, A., Scambia, G., Rustin, G., Stehman, F.B., Gershenson, D., Thomas, G., Berns, E., Casado, A., Ottevanger, N., Hilpert, F., Kim, B.G., Okamoto, A., Bacon, M., Kitchener, H., and Stuart, G.C.

Abstract

Item does not contain fulltext, There is now a greater understanding of the molecular pathways in ovarian cancer, and using this knowledge, a large number of new therapeutic agents can be tested. The success of these drugs will depend on selecting drugs that target known key dysfunctional molecular pathways. To make best use of these compounds, prognostic and predictive biomarkers need to be identified. Novel methods of assessment such as functional imaging need to be developed as additional biological end points to evaluate these therapies. Promising antitumor activity has been observed with some drugs, and careful consideration is needed to determine in what circumstances new agents, such as antiangiogenic compounds, could be considered as a standard therapy. These areas were discussed at the 4th Ovarian Cancer Consensus Conference.

Published
2011

13. Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche

Author

Jing Hua Zhao, Vilmundur Gudnason, Robin Haring, Enda M. Byrne, Christian Gieger, Marek Zygmunt, Lude Franke, Peter Kraft, Eric Boerwinkle, Matthias W. Beckmann, Catharina A. Hartman, Thorkild I. A. Sørensen, Aida Karina Dieffenbach, André G. Uitterlinden, Grant W. Montgomery, Graham G. Giles, Felix R. Day, Anja Rudolph, Arto Mannermaa, Sven Bergmann, Nora Franceschini, Julian Peto, Ellen W. Demerath, Diana L. Cousminer, Wei Ang, Gudmar Thorleifsson, Patrick F. McArdle, Dieter Flesch-Janys, Albertine J. Oldehinkel, Irene L. Andrulis, Aarno Palotie, Nicholas J. Timpson, Paolo Peterlongo, Johan G. Eriksson, Bernardo Bonanni, Dorret I. Boomsma, J. Margriet Collée, Immaculata De Vivo, Bjarke Feenstra, Teresa Ferreira, Cornelia M. van Duijn, Nancy L. Pedersen, Deborah J. Thompson, Peter Vollenweider, Douglas F. Easton, Pascal Guénel, Anna Maria Storniolo, Erik Ingelsson, Gisli Masson, Annika Lindblom, Stefania Bandinelli, Elisabeth Widen, Doris Stöckl, Veikko Salomaa, Zoltán Kutalik, Nicholas J. Wareham, Joanne M. Murabito, Eleonora Porcu, Fergus J. Couch, Katri Pylkäs, Luigi Ferrucci, Wendy L. McArdle, Frank Geller, Andrea D. Coviello, Lynda M. Rose, Daniel L. Koller, Ute Hamann, Ulla Sovio, Daniel F. Gudbjartsson, Georgia Chenevix-Trench, Roger L. Milne, Unnur Thorsteinsdottir, Paul M. Ridker, Henry Völzke, John R. B. Perry, Stephen J. Chanock, Tanguy Corre, Mads Melbye, Ben A. Oostra, Albert V. Smith, Tõnu Esko, Melissa E. Garcia, Debbie A Lawlor, Meir J. Stampfer, Per Hall, Patrick Sulem, Massimo Mangino, Nicholas G. Martin, David J. Hunter, Laura Crisponi, Tatiana Foroud, Antonietta Robino, Michael J. Econs, Susan M. Ring, Natalia Tšernikova, Dirkje S. Postma, Lavinia Paternoster, Peter A. Fasching, Tamara B. Harris, Ellen A. Nohr, Javier Benitez, Ruth J. F. Loos, Robert Winqvist, Andres Metspalu, Jenny A. Visser, Heather A. Boyd, Jonathan Tyrer, Alexander Teumer, Tim D. Spector, Sandra Lai, Douglas P. Kiel, Kamila Czene, Hiltrud Brauch, George Davey Smith, Julia A. Knight, Erin K. Wagner, Suiqun Guo, Tune H. Pers, Patrik K. E. Magnusson, Kathryn L. Lunetta, Hoda Anton-Culver, Marjanka K. Schmidt, George McMahon, Ken K. Ong, Adamo Pio D'Adamo, Veli-Matti Kosma, Jinhui Chen, Paul D.P. Pharoah, Diether Lambrechts, Femke Atsma, Serena Sanna, Ilja M. Nolte, Eco de Geus, Daniel I. Chasman, Emmi Tikkanen, John L. Hopper, Anna Murray, Laura M. Yerges-Armstrong, Sanela Kjellqvist, Eva Albrecht, Hermann Brenner, Paolo Gasparini, Bruce H. R. Wolffenbuttel, Alison M. Dunning, John P. Rice, Craig E. Pennell, Mark I. McCarthy, Andrea Ganna, Henri Wallaschofski, Frank B. Hu, Gérard Waeber, Henrik Flyger, Evelin Mihailov, Peter Devilee, Lisette Stolk, Behrooz Z. Alizadeh, Jouke-Jan Hottenga, Najaf Amin, Patrick Neven, Reedik Mägi, Kyriaki Michailidou, Kari Stefansson, Munro Peacock, Julie E. Buring, Laura J. Bierut, Cathy E. Elks, Marjo-Riitta Järvelin, Montserrat Garcia-Closas, Anneli Pouta, David Schlessinger, Harold Snieder, Chunyan He, Joe Dennis, Heli Nevanlinna, Gonneke Willemsen, Andrew C. Heath, Elizabeth A. Streeten, Albert Hofman, Angela Cox, Maartje J. Hooning, Lili Milani, Margaret J. Wright, Fernando Rivadeneira, Gudny Eiriksdottir, Mellissa C. Southey, Qin Wang, Paolo Radice, Manjeet K. Bolla, Kay-Tee Khaw, Carl Blomqvist, Melanie Waldenberger, Sheila Ulivi, David Couper, Jenny Chang-Claude, David Karasik, Stig E. Bojesen, Andrew D. Johnson, David P. Strachan, Perry, John [0000-0001-6483-3771], Day, Felix [0000-0003-3789-7651], Thompson, Deborah [0000-0003-1465-5799], Zhao, Jing Hua [0000-0003-4930-3582], Dennis, Joe [0000-0003-4591-1214], Dunning, Alison [0000-0001-6651-7166], Pharoah, Paul [0000-0001-8494-732X], Sovio, Ulla [0000-0002-0799-1105], Tyrer, Jonathan [0000-0003-3724-4757], Wang, Jean [0000-0002-9139-0627], Khaw, Kay-Tee [0000-0002-8802-2903], Wareham, Nicholas [0000-0003-1422-2993], Easton, Douglas [0000-0003-2444-3247], Ong, Kenneth [0000-0003-4689-7530], Apollo - University of Cambridge Repository, Australian Ovarian Cancer Study, GENICA Network, kConFab, LifeLines Cohort Study, InterAct Consortium, Early Growth Genetics (EGG) Consortium, Cousminer, D.L., Stergiakouli, E., Berry, D.J., Ang, W., Groen-Blokhuis, M.M., Körner, A., Siitonen, N., Ntalla, I., Marinelli, M., Perry, J.R., Kettunen, J., Jansen, R., Surakka, I., Timpson, N.J., Ring, S., McMahon, G., Power, C., Wang, C., Kähönen, M., Viikari, J., Lehtimäki, T., Middeldorp, C.M., Hulshoff Pol, H.E., Neef, M., Weise, S., Pahkala, K., Niinikoski, H., Zeggini, E., Panoutsopoulou, K., Bustamante, M., Penninx, B.W., Murabito, J., Torrent, M., Dedoussis, G.V., Kiess, W., Boomsma, D.I., Pennell, C.E., Raitakari, O.T., Hyppönen, E., Davey Smith, G., Ripatti, S., McCarthy, M.I., Widén, E., Alizadeh, B.Z., de Boer, R.A., Boezen, H.M., Bruinenberg, M., Franke, L., van der Harst, P., Hillege, H.L., van der Klauw, M.M., Navis, G., Ormel, J., Postma, D., Rosmalen, J.G., Slaets, J.P., Snieder, H., Stolk, R.P., Wolffenbuttel, B.H., Wijmenga, C., Forouhi, N., Kerrison, N.D., Langenberg, C., Scott, R.A., Sharp, S.J., Sims, M., Barroso, I., Deloukas, P., Arriola, L., Balkau, B., Barricarte, A., Boeing, H., Franks, P.W., Gonzalez, C., Grioni, S., Kaaks, R., Key, T.J., Navarro, C., Nilsson, P.M., Overvad, K., Palli, D., Panico, S., Quirós, J., Rolandsson, O., Sacerdote, C., Sánchez, M.J., Slimani, N., Tjonneland, A., Tumino, R., van der A, D.L., van der Schouw, Y.T., Riboli, E., Wareham, N.J., Bowtell, D.D., Green, A., Chenevix-Trench, G., deFazio, A., Gertig, D., Webb, P.M., Brauch, H., Justenhoven, C., Hamann, U., Ko, Y.D., Baisch, C., Fischer, H.P., Pesch, B., Rabstein, S., Spickenheuer, A., Harth, V., Aghmesheh, M., Amor, D., Andrews, L., Antill, Y., Armitage, S., Arnold, L., Balleine, R., Bankier, A., Bastick, P., Beesley, J., Beilby, J., Bennett, I., Bennett, B., Berry, G., Blackburn, A., Bogwitz, M., Brennan, M., Brown, M., Buckley, M., Burgess, M., Burke, J., Butow, P., Byron, K., Callen, D., Campbell, I., Chauhan, D., Christian, A., Clarke, C., Colley, A., Cotton, D., Crook, A., Cui, J., Culling, B., Cummings, M., Dawson, S.J., Delatycki, M., Dickson, R., Dixon, J., Dobrovic, A., Dudding, T., Edkins, T., Edwards, S., Eisenbruch, M., Farshid, G., Fawcett, S., Fellows, A., Fenton, G., Field, M., Firgaira, F., Flanagan, J., Fleming, J., Fong, P., Forbes, J., Fox, S., French, J., Friedlander, M., Gaff, C., Gardner, M., Gattas, M., George, P., Giles, G., Gill, G., Goldblatt, J., Greening, S., Grist, S., Eric, H., Hardie, K., Harris, M., Hart, S., Hayward, N., Healey, S., Heiniger, L., Hopper, J., Humphrey, E., Hunt, C., James, P., Jenkins, M., Jones, A., Kefford, R., Kidd, A., Kiely, B., Kirk, J., Koehler, J., Kollias, J., Kovalenko, S., Lakhani, S., Leaming, A., Leary, J., Lim, J., Lindeman, G., Lipton, L., Lobb, L., Mann, G., Marsh, D., McLachlan, S.A., Meiser, B., Meldrum, C., Milne, R., Mitchell, G., Newman, B., O'Connell, S., O'Loughlin, I., Osborne, R., Pachter, N., Patterson, B., Peters, L., Phillips, K., Price, M., Purser, L., Reeve, J., Reeve, T., Richards, R., Rickard, E., Robinson, B., Rudzki, B., Saleh, M., Salisbury, E., Sambrook, J., Saunders, C., Saunus, J., Sayer, R., Scott, E., Scott, R., Scott, C., Seshadri, R., Sexton, A., Sharma, R., Shelling, A., Simpson, P., Southey, M., Spurdle, A., Suthers, G., Sykes, P., Taylor, D., Taylor, J., Thierry, B., Thompson, E., Thorne, H., Townshend, S., Trainer, A., Tran, L., Tucker, K., Tyler, J., Visvader, J., Walker, L., Walpole, I., Waring, P., Warner, B., Warren, G., Williams, R., Wilson, J., Winship, I., Wu, K., Young, M.A., Public Health, Internal Medicine, Epidemiology, Clinical Genetics, Medical Oncology, Child and Adolescent Psychiatry / Psychology, Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Groningen Research Institute for Asthma and COPD (GRIAC), Lifestyle Medicine (LM), Center for Liver, Digestive and Metabolic Diseases (CLDM), Stem Cell Aging Leukemia and Lymphoma (SALL), Biological Psychology, EMGO+ - Lifestyle, Overweight and Diabetes, Political Science, Perry, John R. B, Day, Felix, Elks, Cathy E, Sulem, Patrick, Thompson, Deborah J, Ferreira, Teresa, He, Chunyan, Chasman, Daniel I, Esko, Tõnu, Thorleifsson, Gudmar, Albrecht, Eva, Ang, Wei Q, Corre, Tanguy, Cousminer, Diana L, Feenstra, Bjarke, Franceschini, Nora, Ganna, Andrea, Johnson, Andrew D, Kjellqvist, Sanela, Lunetta, Kathryn L, Mcmahon, George, Nolte, Ilja M, Paternoster, Lavinia, Porcu, Eleonora, Smith, Albert V, Stolk, Lisette, Teumer, Alexander, Tšernikova, Natalia, Tikkanen, Emmi, Ulivi, Sheila, Wagner, Erin K, Amin, Najaf, Bierut, Laura J, Byrne, Enda M, Hottenga, Jouke Jan, Koller, Daniel L, Mangino, Massimo, Pers, Tune H, Yerges Armstrong, Laura M, Hua Zhao, Jing, Andrulis, Irene L, Anton Culver, Hoda, Atsma, Femke, Bandinelli, Stefania, Beckmann, Matthias W, Benitez, Javier, Blomqvist, Carl, Bojesen, Stig E, Bolla, Manjeet K, Bonanni, Bernardo, Brauch, Hiltrud, Brenner, Hermann, Buring, Julie E, Chang Claude, Jenny, Chanock, Stephen, Chen, Jinhui, Chenevix Trench, Georgia, Collée, J. Margriet, Couch, Fergus J, Couper, David, Coviello, Andrea D, Cox, Angela, Czene, Kamila, D'Adamo, Adamo Pio, Davey Smith, George, De Vivo, Immaculata, Demerath, Ellen W, Dennis, Joe, Devilee, Peter, Dieffenbach, Aida K, Dunning, Alison M, Eiriksdottir, Gudny, Eriksson, Johan G, Fasching, Peter A, Ferrucci, Luigi, Flesch Janys, Dieter, Flyger, Henrik, Foroud, Tatiana, Franke, Lude, Garcia, Melissa E, García Closas, Montserrat, Geller, Frank, de Geus, Eco E. J, Giles, Graham G, Gudbjartsson, Daniel F, Gudnason, Vilmundur, Guénel, Pascal, Guo, Suiqun, Hall, Per, Hamann, Ute, Haring, Robin, Hartman, Catharina A, Heath, Andrew C, Hofman, Albert, Hooning, Maartje J, Hopper, John L, Hu, Frank B, Hunter, David J, Karasik, David, Kiel, Douglas P, Knight, Julia A, Kosma, Veli Matti, Kutalik, Zoltan, Lai, Sandra, Lambrechts, Diether, Lindblom, Annika, Mägi, Reedik, Magnusson, Patrik K, Mannermaa, Arto, Martin, Nicholas G, Masson, Gisli, Mcardle, Patrick F, Mcardle, Wendy L, Melbye, Mad, Michailidou, Kyriaki, Mihailov, Evelin, Milani, Lili, Milne, Roger L, Nevanlinna, Heli, Neven, Patrick, Nohr, Ellen A, Oldehinkel, Albertine J, Oostra, Ben A, Palotie, Aarno, Peacock, Munro, Pedersen, Nancy L, Peterlongo, Paolo, Peto, Julian, Pharoah, Paul D. P, Postma, Dirkje S, Pouta, Anneli, Pylkäs, Katri, Radice, Paolo, Ring, Susan, Rivadeneira, Fernando, Robino, Antonietta, Rose, Lynda M, Rudolph, Anja, Salomaa, Veikko, Sanna, Serena, Schlessinger, David, Schmidt, Marjanka K, Southey, Mellissa C, Sovio, Ulla, Stampfer, Meir J, Stöckl, Dori, Storniolo, Anna M, Timpson, Nicholas J, Tyrer, Jonathan, Visser, Jenny A, Vollenweider, Peter, Völzke, Henry, Waeber, Gerard, Waldenberger, Melanie, Wallaschofski, Henri, Wang, Qin, Willemsen, Gonneke, Winqvist, Robert, Wolffenbuttel, Bruce H. R, Wright, Margaret J, Boomsma, Dorret I, Econs, Michael J, Khaw, Kay Tee, Loos, Ruth J. F, Mccarthy, Mark I, Montgomery, Grant W, Rice, John P, Streeten, Elizabeth A, Thorsteinsdottir, Unnur, van Duijn, Cornelia M, Alizadeh, Behrooz Z, Bergmann, Sven, Boerwinkle, Eric, Boyd, Heather A, Crisponi, Laura, Gasparini, Paolo, Gieger, Christian, Harris, Tamara B, Ingelsson, Erik, Järvelin, Marjo Riitta, Kraft, Peter, Lawlor, Debbie, Metspalu, Andre, Pennell, Craig E, Ridker, Paul M, Snieder, Harold, Sørensen, Thorkild I. A, Spector, Tim D, Strachan, David P, Uitterlinden, André G, Wareham, Nicholas J, Widen, Elisabeth, Zygmunt, Marek, Murray, Anna, Easton, Douglas F, Stefansson, Kari, Murabito, Joanne M, Ong, Ken K., Panico, Salvatore, Perry, John R. B., Elks, Cathy E., Thompson, Deborah J., Chasman, Daniel I., Ang, Wei Q., Cousminer, Diana L., Johnson, Andrew D., Lunetta, Kathryn L., Nolte, Ilja M., Smith, Albert V., Wagner, Erin K., Bierut, Laura J., Byrne, Enda M., Koller, Daniel L., Pers, Tune H., Yerges Armstrong, Laura M., Zhao, Jing Hua, Andrulis, Irene L., Beckmann, Matthias W., Bojesen, Stig E., Bolla, Manjeet K., Buring, Julie E., Couch, Fergus J., Coviello, Andrea D., D'Adamo, ADAMO PIO, Smith, George Davey, Demerath, Ellen W., Dieffenbach, Aida K., Dunning, Alison M., Eriksson, Johan G., Fasching, Peter A., Garcia, Melissa E., De Geus, Eco E. J., Giles, Graham G., Gudbjartsson, Daniel F., Hartman, Catharina A., Heath, Andrew C., Hooning, Maartje J., Hopper, John L., Hu, Frank B., Hunter, David J., Kiel, Douglas P., Knight, Julia A., Magnusson, Patrik K., Martin, Nicholas G., Mcardle, Patrick F., Mcardle, Wendy L., Milne, Roger L., Nohr, Ellen A., Oldehinkel, Albertine J., Oostra, Ben A., Pedersen, Nancy L., Pharoah, Paul D. P., Postma, Dirkje S., Rose, Lynda M., Schmidt, Marjanka K., Southey, Mellissa C., Stampfer, Meir J., Storniolo, Anna M., Timpson, Nicholas J., Visser, Jenny A., Wolffenbuttel, Bruce H. R., Wright, Margaret J., Boomsma, Dorret I., Econs, Michael J., Loos, Ruth J. F., Mccarthy, Mark I., Montgomery, Grant W., Rice, John P., Streeten, Elizabeth A., Van Duijn, Cornelia M., Alizadeh, Behrooz Z., Boyd, Heather A., Harris, Tamara B., Pennell, Craig E., Ridker, Paul M., Sørensen, Thorkild I. A., Spector, Tim D., Strachan, David P., Uitterlinden, André G., Wareham, Nicholas J., Easton, Douglas F., and Murabito, Joanne M.

Subjects
Netherlands Twin Register (NTR), Male, Parents, CENTRAL PRECOCIOUS PUBERTY, Genome-wide association study, Disease, VARIANTS, DISEASE, Body Mass Index, 0302 clinical medicine, Adolescent, Age Factors, Alleles, Breast Neoplasms/genetics, Cardiovascular Diseases/genetics, Child, Diabetes Mellitus, Type 2/genetics, Europe/ethnology, Female, Genetic Loci/genetics, Genome-Wide Association Study, Genomic Imprinting/genetics, Humans, Hypothalamo-Hypophyseal System/physiology, Intercellular Signaling Peptides and Proteins/genetics, Membrane Proteins/genetics, Menarche/genetics, Obesity/genetics, Ovary/physiology, Polymorphism, Single Nucleotide/genetics, Potassium Channels, Tandem Pore Domain/genetics, Proteins/genetics, Quantitative Trait Loci/genetics, Receptors, GABA-B/metabolism, Receptors, Retinoic Acid/metabolism, Ribonucleoproteins/genetics, Intercellular Signaling Peptides and Protein, Age Factor, Tandem Pore Domain, GENE-EXPRESSION, 0303 health sciences, BREAST-CANCER RISK, 3. Good health, Ribonucleoproteins, Cardiovascular Diseases, Menarche, Intercellular Signaling Peptides and Proteins, Science & Technology - Other Topics, GENICA Network, Breast Neoplasm, Type 2, Human, Hypothalamo-Hypophyseal System, Quantitative Trait Loci, Article, 03 medical and health sciences, SDG 3 - Good Health and Well-being, REVEALS, Diabetes Mellitus, Polymorphism, METAANALYSIS, Science & Technology, ta1184, Calcium-Binding Proteins, Proteins, HUMAN PREFRONTAL CORTEX, ta3121, ta3123, Diabetes Mellitus, Type 2, Genetic Loci, CELLS, 030217 neurology & neurosurgery, LifeLines Cohort Study, Potassium Channels, Receptors, Retinoic Acid, Retinoic Acid, Australian Ovarian Cancer Study, Polymorphism (computer science), Cardiovascular Disease, Receptors, WIDE ASSOCIATION, Membrane Protein, Allele, 2. Zero hunger, Genetics, Multidisciplinary, Single Nucleotide, Europe, Multidisciplinary Sciences, kConFab, Breast Neoplasms, Genomic Imprinting, Membrane Proteins, Obesity, Ovary, Polymorphism, Single Nucleotide, Potassium Channels, Tandem Pore Domain, Receptors, GABA-B, General Science & Technology, Ubiquitin-Protein Ligases, Quantitative trait locus, Biology, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], Early Growth Genetics (EGG) Consortium, 030304 developmental biology, Protein, GABA-B, Ribonucleoprotein, InterAct Consortium, Genetic architecture, Parent, Genomic imprinting
Abstract

Contains fulltext : 136472.pdf (Publisher’s version ) (Closed access) Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 x 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and gamma-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.

Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results