PURPOSE: Familial breast cancer represents 5% to 10% of all breast tumors. Mutations in the two known major breast cancer susceptibility genes, BRCA1 and BRCA2, account for a minority of familial breast cancer, whereas families without mutations in these genes (BRCAX group) account for 70% of familial breast cancer cases. EXPERIMENTAL DESIGN: To better characterize and define the genomic differences between the three classes of familial tumors and sporadic malignancies, we have analyzed 19 BRCA1, 24 BRCA2, and 31 BRCAX samples from familial breast cancer patients and 19 sporadic breast tumors using a 1-Mb resolution bacterial artificial chromosome array-based comparative genomic hybridization. RESULTS: We found that BRCA1/2 tumors showed a higher genomic instability than BRCAX and sporadic cancers. There were common genomic alterations present in all breast cancer groups, such as gains of 1q and 16p or losses of 8ptel-p12 and 16q. We found that the presence/absence of the estrogen receptor (ER) may play a crucial role in driving tumor development through distinct genomic pathways independently of the tumor type (sporadic or familial) and mutation status (BRCA1 or BRCA2). ER(-) tumors presented higher genomic instability and different altered regions than ER+ ones. CONCLUSIONS: According to our results, the BRCA gene mutation status (mainly BRCA1) would contribute to the genomic profile of abnormalities by increasing or modulating the genome instability.
PURPOSE:Familial breast cancer represents 5% to 10% of all breast tumors. Mutations in the two known major breast cancer susceptibility genes, BRCA1 and BRCA2, account for a minority of familial breast cancer, whereas families without mutations in these genes (BRCAX group) account for 70% of familial breast cancer cases. EXPERIMENTAL DESIGN: To better characterize and define the genomic differences between the three classes of familial tumors and sporadic malignancies, we have analyzed 19 BRCA1, 24 BRCA2, and 31 BRCAX samples from familial breast cancerpatients and 19 sporadic breast tumors using a 1-Mb resolution bacterial artificial chromosome array-based comparative genomic hybridization. RESULTS: We found that BRCA1/2 tumors showed a higher genomic instability than BRCAX and sporadic cancers. There were common genomic alterations present in all breast cancer groups, such as gains of 1q and 16p or losses of 8ptel-p12 and 16q. We found that the presence/absence of the estrogen receptor (ER) may play a crucial role in driving tumor development through distinct genomic pathways independently of the tumor type (sporadic or familial) and mutation status (BRCA1 or BRCA2). ER(-) tumors presented higher genomic instability and different altered regions than ER+ ones. CONCLUSIONS: According to our results, the BRCA gene mutation status (mainly BRCA1) would contribute to the genomic profile of abnormalities by increasing or modulating the genome instability.
Authors: Nasim Mavaddat; Daniel Barrowdale; Irene L Andrulis; Susan M Domchek; Diana Eccles; Heli Nevanlinna; Susan J Ramus; Amanda Spurdle; Mark Robson; Mark Sherman; Anna Marie Mulligan; Fergus J Couch; Christoph Engel; Lesley McGuffog; Sue Healey; Olga M Sinilnikova; Melissa C Southey; Mary Beth Terry; David Goldgar; Frances O'Malley; Esther M John; Ramunas Janavicius; Laima Tihomirova; Thomas V O Hansen; Finn C Nielsen; Ana Osorio; Alexandra Stavropoulou; Javier Benítez; Siranoush Manoukian; Bernard Peissel; Monica Barile; Sara Volorio; Barbara Pasini; Riccardo Dolcetti; Anna Laura Putignano; Laura Ottini; Paolo Radice; Ute Hamann; Muhammad U Rashid; Frans B Hogervorst; Mieke Kriege; Rob B van der Luijt; Susan Peock; Debra Frost; D Gareth Evans; Carole Brewer; Lisa Walker; Mark T Rogers; Lucy E Side; Catherine Houghton; JoEllen Weaver; Andrew K Godwin; Rita K Schmutzler; Barbara Wappenschmidt; Alfons Meindl; Karin Kast; Norbert Arnold; Dieter Niederacher; Christian Sutter; Helmut Deissler; Doroteha Gadzicki; Sabine Preisler-Adams; Raymonda Varon-Mateeva; Ines Schönbuchner; Heidrun Gevensleben; Dominique Stoppa-Lyonnet; Muriel Belotti; Laure Barjhoux; Claudine Isaacs; Beth N Peshkin; Trinidad Caldes; Miguel de la Hoya; Carmen Cañadas; Tuomas Heikkinen; Päivi Heikkilä; Kristiina Aittomäki; Ignacio Blanco; Conxi Lazaro; Joan Brunet; Bjarni A Agnarsson; Adalgeir Arason; Rosa B Barkardottir; Martine Dumont; Jacques Simard; Marco Montagna; Simona Agata; Emma D'Andrea; Max Yan; Stephen Fox; Timothy R Rebbeck; Wendy Rubinstein; Nadine Tung; Judy E Garber; Xianshu Wang; Zachary Fredericksen; Vernon S Pankratz; Noralane M Lindor; Csilla Szabo; Kenneth Offit; Rita Sakr; Mia M Gaudet; Christian F Singer; Muy-Kheng Tea; Christine Rappaport; Phuong L Mai; Mark H Greene; Anna Sokolenko; Evgeny Imyanitov; Amanda Ewart Toland; Leigha Senter; Kevin Sweet; Mads Thomassen; Anne-Marie Gerdes; Torben Kruse; Maria Caligo; Paolo Aretini; Johanna Rantala; Anna von Wachenfeld; Karin Henriksson; Linda Steele; Susan L Neuhausen; Robert Nussbaum; Mary Beattie; Kunle Odunsi; Lara Sucheston; Simon A Gayther; Kate Nathanson; Jenny Gross; Christine Walsh; Beth Karlan; Georgia Chenevix-Trench; Douglas F Easton; Antonis C Antoniou Journal: Cancer Epidemiol Biomarkers Prev Date: 2011-12-05 Impact factor: 4.254
Authors: Lorenzo Melchor; Laura Paula Saucedo-Cuevas; Iván Muñoz-Repeto; Socorro María Rodríguez-Pinilla; Emiliano Honrado; Alfredo Campoverde; Jose Palacios; Katherine L Nathanson; María José García; Javier Benítez Journal: Breast Cancer Res Date: 2009-12-08 Impact factor: 6.466
Authors: Johan Staaf; Göran Jönsson; Markus Ringnér; Johan Vallon-Christersson; Dorthe Grabau; Adalgeir Arason; Haukur Gunnarsson; Bjarni A Agnarsson; Per-Olof Malmström; Oskar Th Johannsson; Niklas Loman; Rosa B Barkardottir; Ake Borg Journal: Breast Cancer Res Date: 2010-05-06 Impact factor: 6.466