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The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer
Authors :
Figlioli, Gisella Bogliolo, Massimo Catucci, Irene Caleca, Laura Viz Lasheras, Sandra 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 Aittomaki, 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, Paivi Azzollini, Jacopo Balmana, Judith Barkardottir, Rosa B. Barrowdale, Daniel Barwell, Julian Freeman, Laura E. Beane 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 Bruening, Thomas Burwinkel, Barbara Buys, Saundra S. Caldes, 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 Garcia-Closas, Montserrat Garcia-Saenz, Jose A. Gaudet, Mia M. Gayther, Simon A. Giles, Graham G. Glendon, Gord Godwin, Andrew K. Goldberg, Mark S. Goldgar, David E. Guenel, Pascal Gutierrez-Barrera, Angelica M. Haeberle, Lothar Haiman, Christopher A. Hakansson, Niclas Hall, Per Hamann, Ute Harrington, Patricia A. Hein, Alexander Heyworth, Jane Hillemanns, Peter Hollestelle, Antoinette Hopper, John L. Hosgood, H. Dean, III 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, Hakan Osorio, Ana Ottini, Laura Peissel, Bernard Peixoto, Ana Peto, Julian Plaseska-Karanfilska, Dijana Pocza, Timea Presneau, Nadege Angel Pujana, Miquel 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 Santamarina, 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, Therese 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 Doerk, Thilo Schmidt, Marjanka K. Easton, Douglas F. Radice, Paolo Hahnen, Eric Antoniou, Antonis C. Couch, Fergus J. Nevanlinna, Heli Surralles, Jordi Peterlongo, Paolo Balleine, Rosemary Baxter, Robert Braye, Stephen Carpenter, Jane Dahlstrom, Jane Forbes, John Lee, C. Soon Marsh, Deborah Morey, Adrienne Pathmanathan, Nirmala Scott, Rodney Simpson, Peter Spigelman, Allan Wilcken, Nicholas Yip, Desmond Zeps, Nikolajs Belotti, Muriel Bertrand, Ophelie Birot, Anne-Marie Buecher, Bruno Caputo, Sandrine Dupre, Anais Fourme, Emmanuelle Gauthier-Villars, Marion Golmard, Lisa Le Mentec, Marine Moncoutier, Virginie de Pauw, Antoine Saule, Claire Boutry-Kryza, Nadia Calender, Alain Giraud, Sophie Leone, Mlanie Bressac-de-Paillerets, Brigitte Caron, Olivier Guillaud-Bataille, Marine Bignon, Yves-Jean Uhrhammer, Nancy Bonadona, Valerie Lasset, Christine Berthet, Pascaline Castera, Laurent Vaur, Dominique Bourdon, Violaine Nogues, Catherine Noguchi, Tetsuro Popovici, Cornel Remenieras, Audrey Sobol, Hagay Coupier, Isabelle Pujol, Pascal Adenis, Claude Dumont, Aurelie Revillion, Francoise Muller, Daniele Barouk-Simonet, Emmanuelle Bonnet, Francoise Bubien, Virginie Longy, Michel Sevenet, Nicolas Gladieff, Laurence Guimbaud, Rosine Feillel, Viviane Toulas, Christine Dreyfus, Helene Leroux, Christine Dominique Peysselon, Magalie Rebischung, Christine Legrand, Clementine Baurand, Amandine Bertolone, Geoffrey Coron, Fanny Faivre, Laurence Jacquot, Caroline Lizard, Sarab Kientz, Caroline Lebrun, Marine Prieur, Fabienne Fert-Ferrer, Sandra Mari, Vronique Venat-Bouvet, Laurence Bezieau, Stephane Delnatte, Capucine Mortemousque, Isabelle Colas, Chrystelle Coulet, Florence Soubrier, Florent Warcoin, Mathilde Bronner, Myriam Sokolowska, Johanna Collonge-Rame, Marie-Agnes Damette, Alexandre Gesta, Paul Lallaoui, Hakima Chiesa, Jean Molina-Gomes, Denise Ingster, Olivier Manouvrier-Hanu, Sylvie Lejeune, Sophie Aghmesheh, Morteza Greening, Sian Amor, David Gattas, Mike Botes, Leon Buckley, Michael Friedlander, Michael Koehler, Jessica Meiser, Bettina Saleh, Mona Salisbury, Elizabeth Trainer, Alison Tucker, Kathy Antill, Yoland Dobrovic, Alexander Fellows, Andrew Fox, Stephen Harris, Marion Nightingale, Sophie Phillips, Kelly Sambrook, Joe Thorne, Heather Armitage, Shane Arnold, Leanne Kefford, Rick Kirk, Judy Rickard, Edwina Bastick, Patti Beesley, Jonathan Hayward, Nick Spurdle, Amanda Walker, Logan Beilby, John Saunders, Christobel Bennett, Ian Blackburn, Anneke Bogwitz, Michael Gaff, Clara Lindeman, Geoff Pachter, Nick Scott, Clare Sexton, Adrienne Visvader, Jane Taylor, Jessica Winship, Ingrid Brennan, Meagan Brown, Melissa French, Juliet Edwards, Stacey Burgess, Matthew Burke, Jo Patterson, Briony Butow, Phyllis Culling, Bronwyn Caldon, Liz Callen, David Chauhan, Deepa Eisenbruch, Maurice Heiniger, Louise Chauhan, Manisha Christian, Alice Dixon, Joanne Kidd, Alexa Cohen, Paul Colley, Alison Fenton, Georgina Crook, Ashley Dickson, Rebecca Field, Michael Cui, James Cummings, Margaret Dawson, Sarah-Jane DeFazio, Anna Delatycki, Martin Dudding, Tracy Edkins, Ted Farshid, Gelareh Flanagan, James Fong, Peter Forrest, Laura Gallego-Ortega, David George, Peter Gill, Grantley Kollias, James Haan, Eric Hart, Stewart Jenkins, Mark Hunt, Clare Lakhani, Sunil Lipton, Lara Lobb, Liz Mann, Graham McLachlan, Sue Anne O'Connell, Shona O'Sullivan, Sarah Pieper, Ellen Robinson, Bridget Saunus, Jodi Scott, Elizabeth Shelling, Andrew Williams, Rachael Young, Mary Ann Figlioli, Gisella Bogliolo, Massimo Catucci, Irene Caleca, Laura Viz Lasheras, Sandra 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 Aittomaki, 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, Paivi Azzollini, Jacopo Balmana, Judith Barkardottir, Rosa B. Barrowdale, Daniel Barwell, Julian Freeman, Laura E. Beane 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 Bruening, Thomas Burwinkel, Barbara Buys, Saundra S. Caldes, 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 Garcia-Closas, Montserrat Garcia-Saenz, Jose A. Gaudet, Mia M. Gayther, Simon A. Giles, Graham G. Glendon, Gord Godwin, Andrew K. Goldberg, Mark S. Goldgar, David E. Guenel, Pascal Gutierrez-Barrera, Angelica M. Haeberle, Lothar Haiman, Christopher A. Hakansson, Niclas Hall, Per Hamann, Ute Harrington, Patricia A. Hein, Alexander Heyworth, Jane Hillemanns, Peter Hollestelle, Antoinette Hopper, John L. Hosgood, H. Dean, III 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, Hakan Osorio, Ana Ottini, Laura Peissel, Bernard Peixoto, Ana Peto, Julian Plaseska-Karanfilska, Dijana Pocza, Timea Presneau, Nadege Angel Pujana, Miquel 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 Santamarina, 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, Therese 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 Doerk, Thilo Schmidt, Marjanka K. Easton, Douglas F. Radice, Paolo Hahnen, Eric Antoniou, Antonis C. Couch, Fergus J. Nevanlinna, Heli Surralles, Jordi Peterlongo, Paolo Balleine, Rosemary Baxter, Robert Braye, Stephen Carpenter, Jane Dahlstrom, Jane Forbes, John Lee, C. Soon Marsh, Deborah Morey, Adrienne Pathmanathan, Nirmala Scott, Rodney Simpson, Peter Spigelman, Allan Wilcken, Nicholas Yip, Desmond Zeps, Nikolajs Belotti, Muriel Bertrand, Ophelie Birot, Anne-Marie Buecher, Bruno Caputo, Sandrine Dupre, Anais Fourme, Emmanuelle Gauthier-Villars, Marion Golmard, Lisa Le Mentec, Marine Moncoutier, Virginie de Pauw, Antoine Saule, Claire Boutry-Kryza, Nadia Calender, Alain Giraud, Sophie Leone, Mlanie Bressac-de-Paillerets, Brigitte Caron, Olivier Guillaud-Bataille, Marine Bignon, Yves-Jean Uhrhammer, Nancy Bonadona, Valerie Lasset, Christine Berthet, Pascaline Castera, Laurent Vaur, Dominique Bourdon, Violaine Nogues, Catherine Noguchi, Tetsuro Popovici, Cornel Remenieras, Audrey Sobol, Hagay Coupier, Isabelle Pujol, Pascal Adenis, Claude Dumont, Aurelie Revillion, Francoise Muller, Daniele Barouk-Simonet, Emmanuelle Bonnet, Francoise Bubien, Virginie Longy, Michel Sevenet, Nicolas Gladieff, Laurence Guimbaud, Rosine Feillel, Viviane Toulas, Christine Dreyfus, Helene Leroux, Christine Dominique Peysselon, Magalie Rebischung, Christine Legrand, Clementine Baurand, Amandine Bertolone, Geoffrey Coron, Fanny Faivre, Laurence Jacquot, Caroline Lizard, Sarab Kientz, Caroline Lebrun, Marine Prieur, Fabienne Fert-Ferrer, Sandra Mari, Vronique Venat-Bouvet, Laurence Bezieau, Stephane Delnatte, Capucine Mortemousque, Isabelle Colas, Chrystelle Coulet, Florence Soubrier, Florent Warcoin, Mathilde Bronner, Myriam Sokolowska, Johanna Collonge-Rame, Marie-Agnes Damette, Alexandre Gesta, Paul Lallaoui, Hakima Chiesa, Jean Molina-Gomes, Denise Ingster, Olivier Manouvrier-Hanu, Sylvie Lejeune, Sophie Aghmesheh, Morteza Greening, Sian Amor, David Gattas, Mike Botes, Leon Buckley, Michael Friedlander, Michael Koehler, Jessica Meiser, Bettina Saleh, Mona Salisbury, Elizabeth Trainer, Alison Tucker, Kathy Antill, Yoland Dobrovic, Alexander Fellows, Andrew Fox, Stephen Harris, Marion Nightingale, Sophie Phillips, Kelly Sambrook, Joe Thorne, Heather Armitage, Shane Arnold, Leanne Kefford, Rick Kirk, Judy Rickard, Edwina Bastick, Patti Beesley, Jonathan Hayward, Nick Spurdle, Amanda Walker, Logan Beilby, John Saunders, Christobel Bennett, Ian Blackburn, Anneke Bogwitz, Michael Gaff, Clara Lindeman, Geoff Pachter, Nick Scott, Clare Sexton, Adrienne Visvader, Jane Taylor, Jessica Winship, Ingrid Brennan, Meagan Brown, Melissa French, Juliet Edwards, Stacey Burgess, Matthew Burke, Jo Patterson, Briony Butow, Phyllis Culling, Bronwyn Caldon, Liz Callen, David Chauhan, Deepa Eisenbruch, Maurice Heiniger, Louise Chauhan, Manisha Christian, Alice Dixon, Joanne Kidd, Alexa Cohen, Paul Colley, Alison Fenton, Georgina Crook, Ashley Dickson, Rebecca Field, Michael Cui, James Cummings, Margaret Dawson, Sarah-Jane DeFazio, Anna Delatycki, Martin Dudding, Tracy Edkins, Ted Farshid, Gelareh Flanagan, James Fong, Peter Forrest, Laura Gallego-Ortega, David George, Peter Gill, Grantley Kollias, James Haan, Eric Hart, Stewart Jenkins, Mark Hunt, Clare Lakhani, Sunil Lipton, Lara Lobb, Liz Mann, Graham McLachlan, Sue Anne O'Connell, Shona O'Sullivan, Sarah Pieper, Ellen Robinson, Bridget Saunus, Jodi Scott, Elizabeth Shelling, Andrew Williams, Rachael Young, Mary Ann
Publication Year :
2019
Abstract
Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PAM, 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 pArg1931* 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.
Details
Database :
OAIster
Notes :
English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1201313615
Document Type :
Electronic Resource