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| Título: | Inheritance of deleterious mutations at both BRCA1 and BRCA2 in an international sample of 32,295 women |
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| Autor/a: | Rebbeck, Timothy R.; Friebel, Tara M.; Mitra, Nandita; Wan, Fei; Chen, Stephanie; Andrulis, Irene L.; Apostolou, Paraskevi; Arnold, Norbert; Arun, Banu K.; Barrowdale, Daniel; Benitez, Javier; Niederacher, Dieter; Nussbaum, Robert L.; Offit, Kenneth; Olah, Edith; Olopade, Olufunmilayo I.; Kyung Park, Sue; Piedmonte, Marion; Radice, Paolo; Rappaport-Fuerhauser, Christine; Rookus, Matti A.; Seynaeve, Caroline; Simard, Jacques; Singer, Christian F.; Soucy, Penny; Southey, Melissa; Stoppa-Lyonnet, Dominique; Sukiennicki, Grzegorz; Szabo, Csilla I.; Tancredi, Mariella; KConFab Investigators; Teixeira, Manuel R.; Teo, Soo-Hwang; Terry, Mary Beth; Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON); Thomassen, Mads; Tihomirova, Laima; Epidemiological study of BRCA1 & BRCA2 Mutation Carriers (EMBRACE); Tischkowitz, Marc; Ewart Toland, Amanda; Toloczko-Grabarek, Aleksandra; Tung, Nadine; Rensburg, Elizabeth J. van; Villano, Danylo; Wang-Gohrke, Shan; Wappenschmidt, Barbara; Weitzel, Jeffrey N.; Zidan, Jamal; Zorn, Kristin K.; Mcguffog, Lesley; Easton, Douglas; Chenevix-Trench, Georgia; Antoniou, Antonis C.; Ramus, Susan J.; Berger, Raanan; Berthet, Pascaline; Borg, Ake; Buys, Saundra S.; Caldes, Trinidad; Carter, Jonathan; Chiquette, Jocelyne; Claes, Kathleen B. M.; Couch, Fergus J.; Cybulski, Cezary; Daly, Mary B.; Hoya, Miguel de la; Díez Gibert, Orland; Domchek, Susan M.; Nathanson, Katherine L.; Durda, Katarzyna; Ellis, Steve; Evans, D. Gareth; Foretova, Lenka; Friedman, Eitan; Frost, Debra; Ganz, Patricia A.; Garber, Judy; Glendon, Gord; Godwin, Andrew K.; Greene, Mark H.; Gronwald, Jacek; Hahnen, Eric; Hallberg, Emily; Hamann, Ute; Hansen, Thomas V. O.; Imyanitov, Evgeny N.; Isaacs, Claudine; Jakubowska, Anna; Janavicius, Ramunas; Jaworska-Bieniek, Katarzyna; John, Esther M.; Karlan, Beth Y.; Kaufman, Bella; Kwong, Ava; Laitman, Yael; Lasset, Christine; Lázaro García, Conxi; Lester, Jenny; Loman, Niklas; Lubinski, Jan; Manoukian, Siranoush; Mitchell, Gillian; Montagna, Marco; Neuhausen, Susan L.; Nevanlinna, Heli |
| Abstract: | Background: Most BRCA1 or BRCA2 mutation carriers have inherited a single (heterozygous) mutation. Transheterozygotes (TH) who have inherited deleterious mutations in both BRCA1 and BRCA2 are rare, and the consequences of transheterozygosity are poorly understood. Methods: From 32,295 female BRCA1/2 mutation carriers, we identified 93 TH (0.3 %). "Cases" were defined as TH, and "controls" were single mutations at BRCA1 (SH1) or BRCA2 (SH2). Matched SH1 "controls" carried a BRCA1 mutation found in the TH "case". Matched SH2 "controls" carried a BRCA2 mutation found in the TH "case". After matching the TH carriers with SH1 or SH2, 91 TH were matched to 9316 SH1, and 89 TH were matched to 3370 SH2. Results: The majority of TH (45.2 %) involved the three common Jewish mutations. TH were more likely than SH1 and SH2 women to have been ever diagnosed with breast cancer (BC; p = 0.002). TH were more likely to be diagnosed with ovarian cancer (OC) than SH2 (p = 0.017), but not SH1. Age at BC diagnosis was the same in TH vs. SH1 (p = 0.231), but was on average 4.5 years younger in TH than in SH2 (p < 0.001). BC in TH was more likely to be estrogen receptor (ER) positive (p = 0.010) or progesterone receptor (PR) positive (p = 0.013) than in SH1, but less likely to be ER positive (p < 0.001) or PR positive (p = 0.012) than SH2. Among 15 tumors from TH patients, there was no clear pattern of loss of heterozygosity (LOH) for BRCA1 or BRCA2 in either BC or OC. Conclusions: Our observations suggest that clinical TH phenotypes resemble SH1. However, TH breast tumor marker characteristics are phenotypically intermediate to SH1 and SH2. |
| Materia(s): | -Càncer de mama -Breast cancer |
| Derechos: | cc by (c) Rebbeck et al., 2016
http://creativecommons.org/licenses/by/3.0/es/ |
| Tipo de documento: | Artículo Artículo - Versión publicada |
| Editor: | BioMed Central |
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