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Browsing CNIO by Author "Aalfs, Cora M"
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Publication Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations.(Wiley, 2018-05) Rebbeck, Timothy R; Friebel, Tara M; Friedman, Eitan; Hamann, Ute; Huo, Dezheng; Kwong, Ava; Olah, Edith; Olopade, Olufunmilayo I; Solano, Angela R; Teo, Soo-Hwang; Thomassen, Mads; Weitzel, Jeffrey N; Chan, T L; Couch, Fergus J; Goldgar, David E; Kruse, Torben A; Palmero, Edenir Inêz; Park, Sue Kyung; Torres, Diana; van Rensburg, Elizabeth J; McGuffog, Lesley; Parsons, Michael T; Leslie, Goska; Aalfs, Cora M; Abugattas, Julio; Adlard, Julian; Agata, Simona; Aittomäki, Kristiina; Andrews, Lesley; Andrulis, Irene L; Arason, Adalgeir; Arnold, Norbert; Arun, Banu K; Asseryanis, Ella; Auerbach, Leo; Azzollini, Jacopo; Balmaña, Judith; Barile, Monica; Barkardottir, Rosa B; Barrowdale, Daniel; Benitez, Javier; Berger, Andreas; Berger, Raanan; Blanco, Amie M; Blazer, Kathleen R; Blok, Marinus J; Bonadona, Valérie; Bonanni, Bernardo; Bradbury, Angela R; Brewer, Carole; Buecher, Bruno; Buys, Saundra S; Caldes, Trinidad; Caliebe, Almuth; Caligo, Maria A; Campbell, Ian; Caputo, Sandrine M; Chiquette, Jocelyne; Chung, Wendy K; Claes, Kathleen B M; Collée, J Margriet; Cook, Jackie; Davidson, Rosemarie; de la Hoya, Miguel; De Leeneer, Kim; de Pauw, Antoine; Delnatte, Capucine; Diez, Orland; Ding, Yuan Chun; Ditsch, Nina; Domchek, Susan M; Dorfling, Cecilia M; Velazquez, Carolina; Dworniczak, Bernd; Eason, Jacqueline; Easton, Douglas F; Eeles, Ros; Ehrencrona, Hans; Ejlertsen, Bent; Engel, Christoph; Engert, Stefanie; Evans, D Gareth; Faivre, Laurence; Feliubadaló, Lidia; Ferrer, Sandra Fert; Foretova, Lenka; Fowler, Jeffrey; Frost, Debra; Galvão, Henrique C R; Ganz, Patricia A; Garber, Judy; Gauthier-Villars, Marion; Gehrig, Andrea; Gerdes, Anne-Marie; Gesta, Paul; Giannini, Giuseppe; Giraud, Sophie; Glendon, Gord; Godwin, Andrew K; Greene, Mark H; Gronwald, Jacek; Gutierrez-Barrera, Angelica; Hahnen, Eric; Hauke, Jan; Henderson, Alex; Hentschel, Julia; Hogervorst, Frans B L; Honisch, Ellen; Imyanitov, Evgeny N; Isaacs, Claudine; Izatt, Louise; Izquierdo, Angel; Jakubowska, Anna; James, Paul; Janavicius, Ramunas; Jensen, Uffe Birk; John, Esther M; Vijai, Joseph; Kaczmarek, Katarzyna; Karlan, Beth Y; Kast, Karin; Investigators, KConFab; Kim, Sung-Won; Konstantopoulou, Irene; Korach, Jacob; Laitman, Yael; Lasa, Adriana; Lasset, Christine; Lázaro, Conxi; Lee, Annette; Lee, Min Hyuk; Lester, Jenny; Lesueur, Fabienne; Liljegren, Annelie; Lindor, Noralane M; Longy, Michel; Loud, Jennifer T; Lu, Karen H; Lubinski, Jan; Machackova, Eva; Manoukian, Siranoush; Mari, Véronique; Martínez-Bouzas, Cristina; Matrai, Zoltan; Mebirouk, Noura; Meijers-Heijboer, Hanne E J; Meindl, Alfons; Mensenkamp, Arjen R; Mickys, Ugnius; Miller, Austin; Montagna, Marco; Moysich, Kirsten B; Mulligan, Anna Marie; Musinsky, Jacob; Neuhausen, Susan L; Nevanlinna, Heli; Ngeow, Joanne; Nguyen, Huu Phuc; Niederacher, Dieter; Nielsen, Henriette Roed; Nielsen, Finn Cilius; Nussbaum, Robert L; Offit, Kenneth; Öfverholm, Anna; Ong, Kai-Ren; Osorio, Ana; Papi, Laura; Papp, Janos; Pasini, Barbara; Pedersen, Inge Sokilde; Peixoto, Ana; Peruga, Nina; Peterlongo, Paolo; Pohl, Esther; Pradhan, Nisha; Prajzendanc, Karolina; Prieur, Fabienne; Pujol, Pascal; Radice, Paolo; Ramus, Susan J; Rantala, Johanna; Rashid, Muhammad Usman; Rhiem, Kerstin; Robson, Mark; Rodriguez, Gustavo C; Rogers, Mark T; Rudaitis, Vilius; Schmidt, Ane Y; Schmutzler, Rita Katharina; Senter, Leigha; Shah, Payal D; Sharma, Priyanka; Side, Lucy E; Simard, Jacques; Singer, Christian F; Skytte, Anne-Bine; Slavin, Thomas P; Snape, Katie; Sobol, Hagay; Southey, Melissa; Steele, Linda; Steinemann, Doris; Sukiennicki, Grzegorz; Sutter, Christian; Szabo, Csilla I; Tan, Yen Y; Teixeira, Manuel R; Terry, Mary Beth; Teulé, Alex; Thomas, Abigail; Thull, Darcy L; Tischkowitz, Marc; Tognazzo, Silvia; Toland, Amanda Ewart; Topka, Sabine; Trainer, Alison H; Tung, Nadine; van Asperen, Christi J; van der Hout, Annemieke H; van der Kolk, Lizet E; van der Luijt, Rob B; Van Heetvelde, Mattias; Varesco, Liliana; Varon-Mateeva, Raymonda; Vega, Ana; Villarreal-Garza, Cynthia; von Wachenfeldt, Anna; Walker, Lisa; Wang-Gohrke, Shan; Wappenschmidt, Barbara; Weber, Bernhard H F; Yannoukakos, Drakoulis; Yoon, Sook-Yee; Zanzottera, Cristina; Zidan, Jamal; Zorn, Kristin K; Hutten Selkirk, Christina G; Hulick, Peter J; Chenevix-Trench, Georgia; Spurdle, Amanda B; Nathanson, Katherine L; Antoniou, Antonis C; Cancer Research UK (Reino Unido); UK Research and Innovation; National Breast Cancer Foundation (UK)The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been reported in single populations, with the majority of reports focused on White in Europe and North America. The Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) has assembled data on 18,435 families with BRCA1 mutations and 11,351 families with BRCA2 mutations ascertained from 69 centers in 49 countries on six continents. This study comprehensively describes the characteristics of the 1,650 unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations identified in the CIMBA database. We observed substantial variation in mutation type and frequency by geographical region and race/ethnicity. In addition to known founder mutations, mutations of relatively high frequency were identified in specific racial/ethnic or geographic groups that may reflect founder mutations and which could be used in targeted (panel) first pass genotyping for specific populations. Knowledge of the population-specific mutational spectrum in BRCA1 and BRCA2 could inform efficient strategies for genetic testing and may justify a more broad-based oncogenetic testing in some populations.Publication The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer(Nature Publishing Group, 2019-11-01) Figlioli, Gisella; Bogliolo, Massimo; Catucci, Irene; Caleca, Laura; Lasheras, Sandra Viz; Pujol, Roser; Kiiski, Johanna I; Muranen, Taru A; Barnes, Daniel R; Dennis, Joe; Michailidou, Kyriaki; Bolla, Manjeet K; Leslie, Goska; Aalfs, Cora M; Adank, Muriel A; Adlard, Julian; Agata, Simona; Cadoo, Karen; Agnarsson, Bjarni A; Ahearn, Thomas; Aittomäki, Kristiina; Ambrosone, Christine B; Andrews, Lesley; Anton-Culver, Hoda; Antonenkova, Natalia N; Arndt, Volker; Arnold, Norbert; Aronson, Kristan J; Arun, Banu K; Asseryanis, Ella; Auber, Bernd; Auvinen, Päivi; Azzollini, Jacopo; Balmaña, Judith; Barkardottir, Rosa B; Barrowdale, Daniel; Barwell, Julian; Beane Freeman, Laura E; Beauparlant, Charles Joly; Beckmann, Matthias W; Behrens, Sabine; Benitez, Javier; Berger, Raanan; Bermisheva, Marina; Blanco, Amie M; Blomqvist, Carl; Bogdanova, Natalia V; Bojesen, Anders; Bojesen, Stig E; Bonanni, Bernardo; Borg, Ake; Brady, Angela F; Brauch, Hiltrud; Brenner, Hermann; Brüning, Thomas; Burwinkel, Barbara; Buys, Saundra S; Caldés, Trinidad; Caliebe, Almuth; Caligo, Maria A; Campa, Daniele; Campbell, Ian G; Canzian, Federico; Castelao, Jose E; Chang-Claude, Jenny; Chanock, Stephen J; Claes, Kathleen B M; Clarke, Christine L; Collavoli, Anita; Conner, Thomas A; Cox, David G; Cybulski, Cezary; Czene, Kamila; Daly, Mary B; de la Hoya, Miguel; Devilee, Peter; Diez, Orland; Ding, Yuan Chun; Dite, Gillian S; Ditsch, Nina; Domchek, Susan M; Dorfling, Cecilia M; Dos-Santos-Silva, Isabel; Durda, Katarzyna; Dwek, Miriam; Eccles, Diana M; Ekici, Arif B; Eliassen, A Heather; Ellberg, Carolina; Eriksson, Mikael; Evans, D Gareth; Fasching, Peter A; Figueroa, Jonine; Flyger, Henrik; Foulkes, William D; Friebel, Tara M; Friedman, Eitan; Gabrielson, Marike; Gaddam, Pragna; Gago-Dominguez, Manuela; Gao, Chi; Gapstur, Susan M; Garber, Judy; García-Closas, Montserrat; García-Sáenz, José A; Gaudet, Mia M; Gayther, Simon A; Giles, Graham G; Glendon, Gord; Godwin, Andrew K; Goldberg, Mark S; Goldgar, David E; Guénel, Pascal; Gutierrez-Barrera, Angelica M; Haeberle, Lothar; Haiman, Christopher A; Håkansson, Niclas; Hall, Per; Hamann, Ute; Harrington, Patricia A; Hein, Alexander; Heyworth, Jane; Hillemanns, Peter; Hollestelle, Antoinette; Hopper, John L; Hosgood, H Dean; Howell, Anthony; Hu, Chunling; Hulick, Peter J; Hunter, David J; Imyanitov, Evgeny N; Isaacs, Claudine; Jakimovska, Milena; Jakubowska, Anna; James, Paul; Janavicius, Ramunas; Janni, Wolfgang; John, Esther M; Jones, Michael E; Jung, Audrey; Kaaks, Rudolf; Karlan, Beth Y; Khusnutdinova, Elza; Kitahara, Cari M; Konstantopoulou, Irene; Koutros, Stella; Kraft, Peter; Lambrechts, Diether; Lazaro, Conxi; Le Marchand, Loic; Lester, Jenny; Lesueur, Fabienne; Lilyquist, Jenna; Loud, Jennifer T; Lu, Karen H; Luben, Robert N; Lubinski, Jan; Mannermaa, Arto; Manoochehri, Mehdi; Manoukian, Siranoush; Margolin, Sara; Martens, John W M; Maurer, Tabea; Mavroudis, Dimitrios; Mebirouk, Noura; Meindl, Alfons; Menon, Usha; Miller, Austin; Montagna, Marco; Nathanson, Katherine L; Neuhausen, Susan L; Newman, William G; Nguyen-Dumont, Tu; Nielsen, Finn Cilius; Nielsen, Sarah; Nikitina-Zake, Liene; Offit, Kenneth; Olah, Edith; Olopade, Olufunmilayo I; Olshan, Andrew F; Olson, Janet E; Olsson, Håkan; Osorio, Ana; Ottini, Laura; Peissel, Bernard; Peixoto, Ana; Peto, Julian; Plaseska-Karanfilska, Dijana; Pocza, Timea; Presneau, Nadege; Pujana, Miquel Angel; Punie, Kevin; Rack, Brigitte; Rantala, Johanna; Rashid, Muhammad U; Rau-Murthy, Rohini; Rennert, Gad; Lejbkowicz, Flavio; Rhenius, Valerie; Romero, Atocha; Rookus, Matti A; Ross, Eric A; Rossing, Maria; Rudaitis, Vilius; Ruebner, Matthias; Saloustros, Emmanouil; Sanden, Kristin; Santamariña, Marta; Scheuner, Maren T; Schmutzler, Rita K; Schneider, Michael; Scott, Christopher; Senter, Leigha; Shah, Mitul; Sharma, Priyanka; Shu, Xiao-Ou; Simard, Jacques; Singer, Christian F; Sohn, Christof; Soucy, Penny; Southey, Melissa C; Spinelli, John J; Steele, Linda; Stoppa-Lyonnet, Dominique; Tapper, William J; Teixeira, Manuel R; Terry, Mary Beth; Thomassen, Mads; Thompson, Jennifer; Thull, Darcy L; Tischkowitz, Marc; Tollenaar, Rob A E M; Torres, Diana; Troester, Melissa A; Truong, Thérèse; Tung, Nadine; Untch, Michael; Vachon, Celine M; van Rensburg, Elizabeth J; van Veen, Elke M; Vega, Ana; Viel, Alessandra; Wappenschmidt, Barbara; Weitzel, Jeffrey N; Wendt, Camilla; Wieme, Greet; Wolk, Alicja; Yang, Xiaohong R; Zheng, Wei; Ziogas, Argyrios; Zorn, Kristin K; Dunning, Alison M; Lush, Michael; Wang, Qin; McGuffog, Lesley; Parsons, Michael T; Pharoah, Paul D P; Fostira, Florentia; Toland, Amanda E; Andrulis, Irene L; Ramus, Susan J; Swerdlow, Anthony J; Greene, Mark H; Chung, Wendy K; Milne, Roger L; Chenevix-Trench, Georgia; Dörk, Thilo; Schmidt, Marjanka K; Easton, Douglas F; Radice, Paolo; Hahnen, Eric; Antoniou, Antonis C; Couch, Fergus J; Nevanlinna, Heli; Surrallés, Jordi; Peterlongo, Paolo; Ministerio de Economía y Competitividad (España); Unión Europea. Comisión Europea; Against Breast Cancer; Cancer Research UK (Reino Unido); Unión Europea. Comisión Europea. H2020; Cancer UK Grant; Canadian Institutes of Health Research; Ministère de Économie, de la science et de innovation (Canadá); NIH - National Cancer Institute (NCI) (Estados Unidos); Dutch Cancer Society (Holanda); Instituto de Salud Carlos III; Xunta de Galicia (España); Canadian Cancer Society; California Breast Cancer Research Program; California Department of Public Health; Medical Research Council (Reino Unido); Free State of Saxony, Germany (LIFE -Leipzig Research Centre for Civilization Diseases); German Cancer Aid; Helsinki University Hospital; Finlands Akademi (Finlandia); Deutsche Forschungsgemeinschaft (Alemania); Federal Ministry of Education & Research (Alemania); Russian Foundation for Basic Research; Ministry of Science and Higher Education (Rusia); National Health and Medical Research Council (Australia); Biobanking and BioMolecular resources Research Infrastructure (Países Bajos); Estée Lauder Companies’ Breast Cancer Campaign; Swedish Research Council; NIH - National Cancer Institute (NCI). Specialized Programs of Research Excellence (SPOREs) (Estados Unidos); Lon V. Smith Foundation; Lietuvos Mokslo Taryba (Lituania); Italian Association for Cancer Research; University of Kansas. Cancer Center (Estados Unidos); Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); French National Cancer Institute; Netherlands Organisation for Health Research and Development; Pink Ribbons Project; United States Department of Health and Human ServicesBreast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM -/- patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors.