OBJECTIVE: RAD51D, a gene in the Fanconi Anemia-BRCA homologous recombination pathway, has recently been shown to harbor germline mutations responsible for ovarian carcinoma in multiply affected families. We aimed to extend these results to ovarian carcinoma in the general population. METHODS: We sequenced RAD51D in germline DNA from 360 individuals with primary ovarian, peritoneal or fallopian tube carcinoma who were not selected for age of cancer onset or family history. We also sequenced RAD51D in 459 probands from 226 high risk breast cancer families who were wild type for 21 breast and ovarian cancer genes. RESULTS: Of 360 cases, three (0.8%) carried loss-of-function mutations in RAD51D. All three subjects had ovarian carcinoma; one was also diagnosed with a synchronous endometrial carcinoma. Only one of the three subjects had a family history of breast or ovarian cancer. Combined with previous data for this series, 23.9% of women with unselected ovarian, fallopian tube, or peritoneal carcinoma carried a germline loss-of-function mutation in any of 13 tumor suppressor genes. Among the 449 women and 10 men with familial breast cancer, none carried a loss of function mutation in RAD51D. CONCLUSIONS: These data support the previous observation that loss-of-function mutations in RAD51D predispose to ovarian carcinoma but not to breast carcinoma. We conclude that inherited ovarian cancer is highly heterogeneous genetically, and that approximately one in four ovarian carcinoma patients carry a germline mutation in a known tumor suppressor gene that confers high risk.
OBJECTIVE:RAD51D, a gene in the Fanconi Anemia-BRCA homologous recombination pathway, has recently been shown to harbor germline mutations responsible for ovarian carcinoma in multiply affected families. We aimed to extend these results to ovarian carcinoma in the general population. METHODS: We sequenced RAD51D in germline DNA from 360 individuals with primary ovarian, peritoneal or fallopian tube carcinoma who were not selected for age of cancer onset or family history. We also sequenced RAD51D in 459 probands from 226 high risk breast cancer families who were wild type for 21 breast and ovarian cancer genes. RESULTS: Of 360 cases, three (0.8%) carried loss-of-function mutations in RAD51D. All three subjects had ovarian carcinoma; one was also diagnosed with a synchronous endometrial carcinoma. Only one of the three subjects had a family history of breast or ovarian cancer. Combined with previous data for this series, 23.9% of women with unselected ovarian, fallopian tube, or peritoneal carcinoma carried a germline loss-of-function mutation in any of 13 tumor suppressor genes. Among the 449 women and 10 men with familial breast cancer, none carried a loss of function mutation in RAD51D. CONCLUSIONS: These data support the previous observation that loss-of-function mutations in RAD51D predispose to ovarian carcinoma but not to breast carcinoma. We conclude that inherited ovarian cancer is highly heterogeneous genetically, and that approximately one in four ovarian carcinomapatients carry a germline mutation in a known tumor suppressor gene that confers high risk.
Authors: J Y Masson; M C Tarsounas; A Z Stasiak; A Stasiak; R Shah; M J McIlwraith; F E Benson; S C West Journal: Genes Dev Date: 2001-12-15 Impact factor: 11.361
Authors: Tom Walsh; Silvia Casadei; Ming K Lee; Christopher C Pennil; Alex S Nord; Anne M Thornton; Wendy Roeb; Kathy J Agnew; Sunday M Stray; Anneka Wickramanayake; Barbara Norquist; Kathryn P Pennington; Rochelle L Garcia; Mary-Claire King; Elizabeth M Swisher Journal: Proc Natl Acad Sci U S A Date: 2011-10-17 Impact factor: 11.205
Authors: Silvia Casadei; Barbara M Norquist; Tom Walsh; Sunday Stray; Jessica B Mandell; Ming K Lee; John A Stamatoyannopoulos; Mary-Claire King Journal: Cancer Res Date: 2011-02-01 Impact factor: 12.701
Authors: Tom Walsh; Ming K Lee; Silvia Casadei; Anne M Thornton; Sunday M Stray; Christopher Pennil; Alex S Nord; Jessica B Mandell; Elizabeth M Swisher; Mary-Claire King Journal: Proc Natl Acad Sci U S A Date: 2010-06-28 Impact factor: 11.205
Authors: Noah D Kauff; Susan M Domchek; Tara M Friebel; Mark E Robson; Johanna Lee; Judy E Garber; Claudine Isaacs; D Gareth Evans; Henry Lynch; Rosalind A Eeles; Susan L Neuhausen; Mary B Daly; Ellen Matloff; Joanne L Blum; Paul Sabbatini; Richard R Barakat; Clifford Hudis; Larry Norton; Kenneth Offit; Timothy R Rebbeck Journal: J Clin Oncol Date: 2008-02-11 Impact factor: 44.544
Authors: Chey Loveday; Clare Turnbull; Emma Ramsay; Deborah Hughes; Elise Ruark; Jessica R Frankum; Georgina Bowden; Bolot Kalmyrzaev; Margaret Warren-Perry; Katie Snape; Julian W Adlard; Julian Barwell; Jonathan Berg; Angela F Brady; Carole Brewer; Glen Brice; Cyril Chapman; Jackie Cook; Rosemarie Davidson; Alan Donaldson; Fiona Douglas; Lynn Greenhalgh; Alex Henderson; Louise Izatt; Ajith Kumar; Fiona Lalloo; Zosia Miedzybrodzka; Patrick J Morrison; Joan Paterson; Mary Porteous; Mark T Rogers; Susan Shanley; Lisa Walker; Diana Eccles; D Gareth Evans; Anthony Renwick; Sheila Seal; Christopher J Lord; Alan Ashworth; Jorge S Reis-Filho; Antonis C Antoniou; Nazneen Rahman Journal: Nat Genet Date: 2011-08-07 Impact factor: 38.330
Authors: D J Osher; K De Leeneer; G Michils; N Hamel; E Tomiak; B Poppe; K Leunen; E Legius; A Shuen; E Smith; J Arseneau; P Tonin; G Matthijs; K Claes; M D Tischkowitz; W D Foulkes Journal: Br J Cancer Date: 2012-03-13 Impact factor: 7.640
Authors: Kathryn P Pennington; Tom Walsh; Maria I Harrell; Ming K Lee; Christopher C Pennil; Mara H Rendi; Anne Thornton; Barbara M Norquist; Silvia Casadei; Alexander S Nord; Kathy J Agnew; Colin C Pritchard; Sheena Scroggins; Rochelle L Garcia; Mary-Claire King; Elizabeth M Swisher Journal: Clin Cancer Res Date: 2013-11-15 Impact factor: 12.531
Authors: Sarah S Bernards; Barbara M Norquist; Maria I Harrell; Kathy J Agnew; Ming K Lee; Tom Walsh; Elizabeth M Swisher Journal: Gynecol Oncol Date: 2015-12-21 Impact factor: 5.482
Authors: Mariam M AlHilli; Marc A Becker; S John Weroha; Karen S Flatten; Rachel M Hurley; Maria I Harrell; Ann L Oberg; Matt J Maurer; Kieran M Hawthorne; Xiaonan Hou; Sean C Harrington; Sarah McKinstry; X Wei Meng; Keith M Wilcoxen; Kimberly R Kalli; Elizabeth M Swisher; Scott H Kaufmann; Paul Haluska Journal: Gynecol Oncol Date: 2016-09-08 Impact factor: 5.482
Authors: Ciyu Yang; Angela G Arnold; Amanda Catchings; Vikas Rai; Zsofia K Stadler; Liying Zhang Journal: Breast Cancer Res Treat Date: 2021-01-16 Impact factor: 4.872
Authors: Marketa Janatova; Jana Soukupova; Jana Stribrna; Petra Kleiblova; Michal Vocka; Petra Boudova; Zdenek Kleibl; Petr Pohlreich Journal: PLoS One Date: 2015-06-09 Impact factor: 3.240
Authors: Ella R Thompson; Simone M Rowley; Sarah Sawyer; Diana M Eccles; Alison H Trainer; Gillian Mitchell; Paul A James; Ian G Campbell Journal: PLoS One Date: 2013-01-25 Impact factor: 3.240
Authors: Honglin Song; Ed Dicks; Susan J Ramus; Jonathan P Tyrer; Maria P Intermaggio; Jane Hayward; Christopher K Edlund; David Conti; Patricia Harrington; Lindsay Fraser; Susan Philpott; Christopher Anderson; Adam Rosenthal; Aleksandra Gentry-Maharaj; David D Bowtell; Kathryn Alsop; Mine S Cicek; Julie M Cunningham; Brooke L Fridley; Jennifer Alsop; Mercedes Jimenez-Linan; Estrid Høgdall; Claus K Høgdall; Allan Jensen; Susanne Krüger Kjaer; Jan Lubiński; Tomasz Huzarski; Anna Jakubowska; Jacek Gronwald; Samantha Poblete; Shashi Lele; Lara Sucheston-Campbell; Kirsten B Moysich; Kunle Odunsi; Ellen L Goode; Usha Menon; Ian J Jacobs; Simon A Gayther; Paul D P Pharoah Journal: J Clin Oncol Date: 2015-08-10 Impact factor: 44.544