FANCM c.5791C>T nonsense mutation (rs144567652) induces exon skipping, affects DNA repair activity and is a familial breast cancer risk factor

Peterlongo, Paolo, Catucci, Irene, Colombo, Mara, Caleca, Laura, Mucaki, Eliseos, Bogliolo, Massimo, Marin, Maria, Damiola, Francesca, Bernard, Loris, Pensotti, Valeria, Volorio, Sara, Dall'Olio, Valentina, Meindl, Alfons, Bartram, Claus, Sutter, Christian, Surowy, Harald, Sornin, Valerie, Dondon, Marie-Gabrielle, Eon-Marchais, Severine, Stoppa-Lyonnet, Dominique, Andrieu, Nadine, Sinilnikova, Olga M., Mitchell, Gillian, James, Paul A., Thompson, Ella, Marchetti, Marina, Verzeroli, Cristina, Tartari, Carmen, Capone, Gabriele Lorenzo, Putignano, Anna Laura, Genuardi, Maurizio, Medici, Veronica, Marchi, Isabella, Federico, Massimo, Tognazzo, Silvia, Matricardi, Laura, Agata, Simona, Dolcetti, Riccardo, Della Puppa, Lara, Cini, Giulia, Gismondi, Viviana, Viassolo, Valeria, Perfumo, Chiara, Mencarelli, Maria Antonietta, Baldassarri, Margherita, Peissel, Bernard, Roversi, Gaia, Silvestri, Valentina, Rizzolo, Piera, Spina, Francesca, Vivanet, Caterina, Tibiletti, Maria Grazia, Caligo, Maria Adelaide, Gambino, Gaetana, Tommasi, Stefania, Pilato, Brunella, Tondini, Carlo, Corna, Chiara, Bonanni, Bernardo, Barile, Monica, Osorio, Ana, Benitez, Javier, Balestrino, Luisa, Ottini, Laura, Manoukian, Siranoush, Pierotti, Marco A., Renieri, Alessandra, Varesco, Liliana, Couch, Fergus J., Wang, Xianshu, Devilee, Peter, Hilbers, Florentine S., van Asperen, Christi J., Viel, Alessandra, Montagna, Marco, Cortesi, Laura, Diez, Orland, Balmana, Judith, Hauke, Jan, Schmutzler, Rita K., Papi, Laura, Angel Pujana, Miguel, Lazaro, Conxi, Falanga, Anna, Offit, Kenneth, Vijai, Joseph, Campbell, Ian, Burwinkel, Barbara, Kvist, Anders, Ehrencrona, Hans, Mazoyer, Sylvie, Pizzamiglio, Sara, Verderio, Paolo, Surralles, Jordi, Rogan, Peter K. and Radice, Paolo (2015) FANCM c.5791C>T nonsense mutation (rs144567652) induces exon skipping, affects DNA repair activity and is a familial breast cancer risk factor. Human Molecular Genetics, 24 18: 5345-5355. doi:10.1093/hmg/ddv251


Author Peterlongo, Paolo
Catucci, Irene
Colombo, Mara
Caleca, Laura
Mucaki, Eliseos
Bogliolo, Massimo
Marin, Maria
Damiola, Francesca
Bernard, Loris
Pensotti, Valeria
Volorio, Sara
Dall'Olio, Valentina
Meindl, Alfons
Bartram, Claus
Sutter, Christian
Surowy, Harald
Sornin, Valerie
Dondon, Marie-Gabrielle
Eon-Marchais, Severine
Stoppa-Lyonnet, Dominique
Andrieu, Nadine
Sinilnikova, Olga M.
Mitchell, Gillian
James, Paul A.
Thompson, Ella
Marchetti, Marina
Verzeroli, Cristina
Tartari, Carmen
Capone, Gabriele Lorenzo
Putignano, Anna Laura
Genuardi, Maurizio
Medici, Veronica
Marchi, Isabella
Federico, Massimo
Tognazzo, Silvia
Matricardi, Laura
Agata, Simona
Dolcetti, Riccardo
Della Puppa, Lara
Cini, Giulia
Gismondi, Viviana
Viassolo, Valeria
Perfumo, Chiara
Mencarelli, Maria Antonietta
Baldassarri, Margherita
Peissel, Bernard
Roversi, Gaia
Silvestri, Valentina
Rizzolo, Piera
Spina, Francesca
Vivanet, Caterina
Tibiletti, Maria Grazia
Caligo, Maria Adelaide
Gambino, Gaetana
Tommasi, Stefania
Pilato, Brunella
Tondini, Carlo
Corna, Chiara
Bonanni, Bernardo
Barile, Monica
Osorio, Ana
Benitez, Javier
Balestrino, Luisa
Ottini, Laura
Manoukian, Siranoush
Pierotti, Marco A.
Renieri, Alessandra
Varesco, Liliana
Couch, Fergus J.
Wang, Xianshu
Devilee, Peter
Hilbers, Florentine S.
van Asperen, Christi J.
Viel, Alessandra
Montagna, Marco
Cortesi, Laura
Diez, Orland
Balmana, Judith
Hauke, Jan
Schmutzler, Rita K.
Papi, Laura
Angel Pujana, Miguel
Lazaro, Conxi
Falanga, Anna
Offit, Kenneth
Vijai, Joseph
Campbell, Ian
Burwinkel, Barbara
Kvist, Anders
Ehrencrona, Hans
Mazoyer, Sylvie
Pizzamiglio, Sara
Verderio, Paolo
Surralles, Jordi
Rogan, Peter K.
Radice, Paolo
Title FANCM c.5791C>T nonsense mutation (rs144567652) induces exon skipping, affects DNA repair activity and is a familial breast cancer risk factor
Journal name Human Molecular Genetics   Check publisher's open access policy
ISSN 1460-2083
0964-6906
Publication date 2015-04-09
Sub-type Article (original research)
DOI 10.1093/hmg/ddv251
Open Access Status Not Open Access
Volume 24
Issue 18
Start page 5345
End page 5355
Total pages 11
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Collection year 2016
Language eng
Abstract Numerous genetic factors that influence breast cancer risk are known. However, approximately two-thirds of the overall familial risk remain unexplained. To determine whether some of the missing heritability is due to rare variants conferring high to moderate risk, we tested for an association between the c.5791C>T nonsense mutation (p.Arg1931*; rs144567652) in exon 22 of FANCM gene and breast cancer. An analysis of genotyping data from 8635 familial breast cancer cases and 6625 controls from different countries yielded an association between the c.5791C>T mutation and breast cancer risk [odds ratio (OR) = 3.93 (95% confidence interval (CI) = 1.28–12.11; P = 0.017)]. Moreover, we performed two meta-analyses of studies from countries with carriers in both cases and controls and of all available data. These analyses showed breast cancer associations with OR = 3.67 (95% CI = 1.04–12.87; P = 0.043) and OR = 3.33 (95% CI = 1.09–13.62; P = 0.032), respectively. Based on information theory-based prediction, we established that the mutation caused an out-of-frame deletion of exon 22, due to the creation of a binding site for the pre-mRNA processing protein hnRNP A1. Furthermore, genetic complementation analyses showed that the mutation influenced the DNA repair activity of the FANCM protein. In summary, we provide evidence for the first time showing that the common p.Arg1931* loss-of-function variant in FANCM is a risk factor for familial breast cancer.
Q-Index Code CX
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
UQ Diamantina Institute Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 8 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 8 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Fri, 27 Nov 2015, 19:50:37 EST by System User on behalf of Scholarly Communication and Digitisation Service