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

Peterlongo, Paolo (author)
Catucci, Irene (author)
Colombo, Mara (author)
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Caleca, Laura (author)
Mucaki, Eliseos (author)
Bogliolo, Massimo (author)
Marin, Maria (author)
Damiola, Francesca (author)
Bernard, Loris (author)
Pensotti, Valeria (author)
Volorio, Sara (author)
Dall'Olio, Valentina (author)
Meindl, Alfons (author)
Bartram, Claus (author)
Sutter, Christian (author)
Surowy, Harald (author)
Sornin, Valérie (author)
Dondon, Marie-Gabrielle (author)
Eon-Marchais, Séverine (author)
Stoppa-Lyonnet, Dominique (author)
Andrieu, Nadine (author)
Sinilnikova, Olga M (author)
Mitchell, Gillian (author)
James, Paul A (author)
Thompson, Ella (author)
Marchetti, Marina (author)
Verzeroli, Cristina (author)
Tartari, Carmen (author)
Capone, Gabriele Lorenzo (author)
Putignano, Anna Laura (author)
Genuardi, Maurizio (author)
Medici, Veronica (author)
Marchi, Isabella (author)
Federico, Massimo (author)
Tognazzo, Silvia (author)
Matricardi, Laura (author)
Agata, Simona (author)
Dolcetti, Riccardo (author)
Puppa, Lara Della (author)
Cini, Giulia (author)
Gismondi, Viviana (author)
Viassolo, Valeria (author)
Perfumo, Chiara (author)
Mencarelli, Maria Antonietta (author)
Baldassarri, Margherita (author)
Peissel, Bernard (author)
Roversi, Gaia (author)
Silvestri, Valentina (author)
Rizzolo, Piera (author)
Spina, Francesca (author)
Vivanet, Caterina (author)
Tibiletti, Maria Grazia (author)
Caligo, Maria Adelaide (author)
Gambino, Gaetana (author)
Tommasi, Stefania (author)
Pilato, Brunella (author)
Tondini, Carlo (author)
Corna, Chiara (author)
Bonanni, Bernardo (author)
Barile, Monica (author)
Osorio, Ana (author)
Benitez, Javier (author)
Balestrino, Luisa (author)
Ottini, Laura (author)
Manoukian, Siranoush (author)
Pierotti, Marco A (author)
Renieri, Alessandra (author)
Varesco, Liliana (author)
Couch, Fergus J (author)
Wang, Xianshu (author)
Devilee, Peter (author)
Hilbers, Florentine S (author)
van Asperen, Christi J (author)
Viel, Alessandra (author)
Montagna, Marco (author)
Cortesi, Laura (author)
Diez, Orland (author)
Balmaña, Judith (author)
Hauke, Jan (author)
Schmutzler, Rita K (author)
Papi, Laura (author)
Pujana, Miguel Angel (author)
Lázaro, Conxi (author)
Falanga, Anna (author)
Offit, Kenneth (author)
Vijai, Joseph (author)
Campbell, Ian (author)
Burwinkel, Barbara (author)
Kvist, Anders (author)
Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Familjär bröstcancer,Forskargrupper vid Lunds universitet,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Familial Breast Cancer,Lund University Research Groups
Ehrencrona, Hans (author)
Lund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine
Mazoyer, Sylvie (author)
Pizzamiglio, Sara (author)
Verderio, Paolo (author)
Surralles, Jordi (author)
Rogan, Peter K (author)
Radice, Paolo (author)
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 (creator_code:org_t)
2015-06-30
2015
English.
In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:18, s. 5345-5355
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

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Peterlongo, Paol ...
Catucci, Irene
Colombo, Mara
Caleca, Laura
Mucaki, Eliseos
Bogliolo, Massim ...
show more...
Marin, Maria
Damiola, Frances ...
Bernard, Loris
Pensotti, Valeri ...
Volorio, Sara
Dall'Olio, Valen ...
Meindl, Alfons
Bartram, Claus
Sutter, Christia ...
Surowy, Harald
Sornin, Valérie
Dondon, Marie-Ga ...
Eon-Marchais, Sé ...
Stoppa-Lyonnet, ...
Andrieu, Nadine
Sinilnikova, Olg ...
Mitchell, Gillia ...
James, Paul A
Thompson, Ella
Marchetti, Marin ...
Verzeroli, Crist ...
Tartari, Carmen
Capone, Gabriele ...
Putignano, Anna ...
Genuardi, Mauriz ...
Medici, Veronica
Marchi, Isabella
Federico, Massim ...
Tognazzo, Silvia
Matricardi, Laur ...
Agata, Simona
Dolcetti, Riccar ...
Puppa, Lara Dell ...
Cini, Giulia
Gismondi, Vivian ...
Viassolo, Valeri ...
Perfumo, Chiara
Mencarelli, Mari ...
Baldassarri, Mar ...
Peissel, Bernard
Roversi, Gaia
Silvestri, Valen ...
Rizzolo, Piera
Spina, Francesca
Vivanet, Caterin ...
Tibiletti, Maria ...
Caligo, Maria Ad ...
Gambino, Gaetana
Tommasi, Stefani ...
Pilato, Brunella
Tondini, Carlo
Corna, Chiara
Bonanni, Bernard ...
Barile, Monica
Osorio, Ana
Benitez, Javier
Balestrino, Luis ...
Ottini, Laura
Manoukian, Siran ...
Pierotti, Marco ...
Renieri, Alessan ...
Varesco, Liliana
Couch, Fergus J
Wang, Xianshu
Devilee, Peter
Hilbers, Florent ...
van Asperen, Chr ...
Viel, Alessandra
Montagna, Marco
Cortesi, Laura
Diez, Orland
Balmaña, Judith
Hauke, Jan
Schmutzler, Rita ...
Papi, Laura
Pujana, Miguel A ...
Lázaro, Conxi
Falanga, Anna
Offit, Kenneth
Vijai, Joseph
Campbell, Ian
Burwinkel, Barba ...
Kvist, Anders
Ehrencrona, Hans
Mazoyer, Sylvie
Pizzamiglio, Sar ...
Verderio, Paolo
Surralles, Jordi
Rogan, Peter K
Radice, Paolo
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MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Clinical Medicin ...
and Cancer and Oncol ...
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Human Molecular ...
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Lund University

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