Resum
Idioma original | Anglès |
---|---|
Revista | npj Breast Cancer |
Volum | 5 |
DOIs | |
Estat de la publicació | Publicada - 2019 |
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In: npj Breast Cancer, Vol. 5, 2019.
Producció científica: Contribució a revista › Article › Recerca › Avaluat per experts
TY - JOUR
T1 - The FANCM :p.Arg658* truncating variant is associated with risk of triple-negative breast cancer
AU - Bogliolo, Massimo
AU - Surrallés i Calonge, Jordi
AU - Figlioli, Gisella
AU - Catucci, Irene
AU - Caleca, Laura
AU - Viz Lasheras, Sandra
AU - Pujol, Roser
AU - Kiiski, Johanna I.
AU - Muranen, Taru A.
AU - Barnes, Daniel R.
AU - Dennis, Joe
AU - Michailidou, Kyriaki
AU - Bolla, Manjeet K.
AU - Leslie, Goska
AU - Aalfs, Cora M.
AU - Adank, Muriel A.
AU - Adlard, Julian
AU - Agata, Simona
AU - Cadoo, Karen
AU - Agnarsson, Bjarni A.
AU - Ahearn, Thomas
AU - Aittomäki, Kristiina
AU - Ambrosone, Christine B.
AU - Andrews, Lesley
AU - Anton-Culver, Hoda
AU - Antonenkova, Natalia N.
AU - Arndt, Volker
AU - Arnold, Norbert
AU - Aronson, Kristan J.
AU - Arun, Banu K.
AU - Asseryanis, Ella
AU - Auber, Bernd
AU - Auvinen, Päivi
AU - Azzollini, Jacopo
AU - Balmaña Gelpí, Judith
AU - Barkardottir, Rosa B.
AU - Barrowdale, Daniel
AU - Barwell, Julian
AU - Beane Freeman, Laura E.
AU - Beauparlant, Charles Joly
AU - Beckmann, Matthias W.
AU - Behrens, Sabine
AU - Benitez, Javier
AU - Berger, Raanan
AU - Bermisheva, Marina
AU - Blanco, Amie M.
AU - Blomqvist, Carl
AU - Bogdanova, Natalia V.
AU - Bojesen, Anders
AU - Bojesen, Stig E.
AU - Bonanni, Bernardo
AU - Borg, Åke
AU - Brady, Angela F.
AU - Brauch, Hiltrud
AU - Brenner, Hermann
AU - Brüning, Thomas
AU - Burwinkel, Barbara
AU - Buys, Saundra
AU - Caldes, Trinidad
AU - Caliebe, Almuth
AU - Caligo, Maria
AU - Campa, Daniele
AU - Campbell, Ian
AU - Canzian, Federico
AU - Castelao, Jose E.
AU - Chang-Claude, Jenny
AU - Chanock, Stephen J.
AU - Claes, Kathleen
AU - Clarke, Christine L.
AU - Collavoli, Anita
AU - Conner, Thomas A.
AU - Cox, David G.
AU - Cybulski, Cezary
AU - Czene, Kamila
AU - Daly, Mary B.
AU - De la Hoya, Miguel
AU - Devilee, Peter
AU - Diez, Orland
AU - Ding, Yuan Chun
AU - Dite, Gillian S.
AU - Ditsch, Nina
AU - Domchek, Susan M.
AU - Dorfling, Cecilia M.
AU - dos-Santos-Silva, Isabel
AU - Durda, Katarzyna
AU - Dwek, Miriam
AU - Eccles, Diana M.
AU - Ekici, Arif B.
AU - Eliassen, A. Heather
AU - Ellberg, Carolina
AU - Eriksson, Mikael
AU - Evans, D. Gareth
AU - Fasching, Peter A.
AU - Figueroa, Jonine
AU - Flyger, Henrik
AU - Foulkes, William D.
AU - Friebel, Tara M.
AU - Friedman, Eitan
AU - Gabrielson, Marike
AU - Gaddam, Pragna
AU - Gago-Dominguez, Manuela
AU - Gao, Chi
AU - Gapstur, Susan M.
AU - Garber, Judy
AU - García-Closas, Montserrat
AU - García-Sáenz, José A.
AU - Gaudet, Mia M.
AU - Gayther, Simon A.
AU - Giles, Graham G.
AU - Glendon, Gord
AU - Godwin, Andrew K.
AU - Goldberg, Mark S.
AU - Goldgar, David E.
AU - Guénel, Pascal
AU - Gutierrez-Barrera, Angelica M.
AU - Haeberle, Lothar
AU - Haiman, Christopher A.
AU - Håkansson, Niclas
AU - Hall, Per
AU - Hamann, Ute
AU - Harrington, Patricia A.
AU - Hein, Alexander
AU - Heyworth, Jane
AU - Hillemanns, Peter
AU - Hollestelle, Antoinette
AU - Hopper, John L.
AU - Hosgood, H. Dean
AU - Howell, Anthony
AU - Hu, Chunling
AU - Hulick, Peter J.
AU - Hunter, David J.
AU - Imyanitov, Evgeny N.
AU - Isaacs, Claudine
AU - Jakimovska, Milena
AU - Jakubowska, Anna
AU - James, Paul
AU - Janavicius, Ramunas
AU - Janni, Wolfgang
AU - John, Esther M.
AU - Jones, Michael E.
AU - Jung, Audrey
AU - Kaaks, Rudolf
AU - Karlan, Beth Y.
AU - Khusnutdinova, Elza
AU - Kitahara, Cari M.
AU - Konstantopoulou, Irene
AU - Koutros, Stella
AU - Kraft, Peter
AU - Lambrechts, Diether
AU - Lazaro, Conxi
AU - Le Marchand, Loic
AU - Lester, Jenny
AU - Lesueur, Fabienne
AU - Lilyquist, Jenna
AU - Loud, Jennifer T.
AU - Lu, Karen H.
AU - Luben, Robert N.
AU - Lubinski, Jan
AU - Mannermaa, Arto
AU - Manoochehri, Mehdi
AU - Manoukian, Siranoush
AU - Margolin, Sara
AU - Martens, John W. M.
AU - Maurer, Tabea
AU - Mavroudis, Dimitrios
AU - Mebirouk, Noura
AU - Meindl, Alfons
AU - Menon, Usha
AU - Miller, Austin
AU - Montagna, Marco
AU - Nathanson, Katherine L.
AU - Neuhausen, Susan L.
AU - Newman, William G.
AU - Nguyen-Dumont, Tu
AU - Nielsen, Finn Cilius
AU - Nielsen, Sarah
AU - Nikitina-Zake, Liene
AU - Offit, Kenneth
AU - Olah, Edith
AU - Olopade, Olufunmilayo I.
AU - Olshan, Andrew F.
AU - Olson, Janet E.
AU - Olsson, Håkan
AU - Osorio, Ana
AU - Ottini, Laura
AU - Peissel, Bernard
AU - Peixoto, Ana
AU - Peto, Julian
AU - Plaseska-Karanfilska, Dijana
AU - Pocza, Timea
AU - Presneau, Nadege
AU - Pujana, Miquel Angel
AU - Punie, Kevin
AU - Rack, Brigitte
AU - Rantala, Johanna
AU - Rashid, Muhammad U.
AU - Rau-Murthy, Rohini
AU - Rennert, Gad
AU - Lejbkowicz, Flavio
AU - Rhenius, Valerie
AU - Romero, Atocha
AU - Rookus, Matti A.
AU - Ross, Eric A.
AU - Rossing, Maria
AU - Rudaitis, Vilius
AU - Ruebner, Matthias
AU - Saloustros, Emmanouil
AU - Sanden, Kristin
AU - Santamariña, Marta
AU - Scheuner, Maren T.
AU - Schmutzler, Rita K.
AU - Schneider, Michael
AU - Scott, Christopher
AU - Senter, Leigha
AU - Shah, Mitul
AU - Sharma, Priyanka
AU - Shu, Xiao-Ou
AU - Simard, Jacques
AU - Singer, Christian F.
AU - Sohn, Christof
AU - Soucy, Penny
AU - Southey, Melissa C.
AU - Spinelli, John J.
AU - Steele, Linda
AU - Stoppa-Lyonnet, Dominique
AU - Tapper, William J.
AU - Teixeira, Manuel R.
AU - Terry, Mary Beth
AU - Thomassen, Mads
AU - Thompson, Jennifer
AU - Thull, Darcy L.
AU - Tischkowitz, Marc
AU - Tollenaar, Rob A. E. M.
AU - Torres, Diana
AU - Troester, Melissa A.
AU - Truong, Thérèse
AU - Tung, Nadine
AU - Untch, Michael
AU - Vachon, Celine M.
AU - van Rensburg, Elizabeth J.
AU - van Veen, Elke M.
AU - Vega, Ana
AU - Viel, Alessandra
AU - Wappenschmidt, Barbara
AU - Weitzel, Jeffrey N.
AU - Wendt, Camilla
AU - Wieme, Greet
AU - Wolk, Alicja
AU - Yang, Xiaohong R.
AU - Zheng, Wei
AU - Ziogas, Argyrios
AU - Zorn, Kristin K.
AU - Dunning, Alison M.
AU - Lush, Michael
AU - Wang, Qin
AU - McGuffog, Lesley
AU - Parsons, Michael T.
AU - Pharoah, Paul D. P.
AU - Fostira, Florentia
AU - Toland, Amanda E.
AU - Andrulis, Irene L.
AU - Ramus, Susan J.
AU - Swerdlow, Anthony J.
AU - Greene, Mark H.
AU - Chung, Wendy K.
AU - Milne, Roger L.
AU - Chenevix-Trench, Georgia
AU - Dörk, Thilo
AU - Schmidt, Marjanka K.
AU - Easton, Douglas F.
AU - Radice, Paolo
AU - Hahnen, Eric
AU - Antoniou, Antonis C.
AU - Couch, Fergus J.
AU - Nevanlinna, Heli
AU - Peterlongo, Paolo
PY - 2019
Y1 - 2019
N2 - Breast 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.
AB - Breast 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.
KW - Cancer genetics
U2 - 10.1038/s41523-019-0127-5
DO - 10.1038/s41523-019-0127-5
M3 - Article
C2 - 31700994
SN - 2374-4677
VL - 5
JO - npj Breast Cancer
JF - npj Breast Cancer
ER -