Introduction: Breast cancer (BC) in men is a rare disease, whose etiology appears to be associated with genetic factors. Inherited mutations in BRCA1/2 genes account for about 10e15% of all cases. FANCM, functionally linked to BRCA1/2, has been suggested as a novel BC susceptibility gene. Our aim was to test if FANCM germline mutations could further explain male BC (MBC) susceptibility. Methods: We screened the entire coding region of FANCM in 286 MBCs by a multi-gene panel analysis, and compared these data with available whole exome sequencing data from 415 men used as population controls. Moreover, we genotyped the two most frequent FANCM mutations (c.5101C>T and c.5791C>T) in 506 MBCs and 854 healthy male controls. Results: Two FANCM truncating mutations, the c.1432C>T (p.Arg478Ter) and c.1972C>T (p.Arg658Ter), were identified in two MBC cases (0.7%). When specifically considering cases at increased genetic risk for BC, FANCM mutation frequency raises up to 1%. One mutation, the c.2201_2202delCT (p.Ser734Terfs), was found among controls (0.24%). Mutation frequency in cases was higher than in controls, however this difference was not statistically significant. FANCM c.5101C>T was not present in any of the cases and controls analyzed, whereas FANCM c.5791C>T was found in two controls (0.23%). Conclusion: Rare FANCM truncating mutations, other than c.5101C>T and c.5791C>T, may have a role in MBC susceptibility. The inclusion of FANCM in gene panels for research purpose would allow for the identification of a higher number of mutation carriers, thus helping estimate BC risk associated with FANCM mutations.

A possible role of FANCM mutations in male breast cancer susceptibility: Results from a multicenter study in Italy / Silvestri, Valentina; Rizzolo, Piera; Zelli, Veronica; Valentini, Virginia; Zanna, Ines; Bianchi, Simonetta; Tibiletti, Maria Grazia; Varesco, Liliana; Russo, Antonio; Tommasi, Stefania; Coppa, Anna; Capalbo, Carlo; Calistri, Daniele; Viel, Alessandra; Cortesi, Laura; Manoukian, Siranoush; Bonanni, Bernardo; Montagna, Marco; Palli, Domenico; Radice, Paolo; Peterlongo, Paolo; Ottini, Laura*. - In: THE BREAST. - ISSN 0960-9776. - ELETTRONICO. - 38:(2018), pp. 92-97. [10.1016/j.breast.2017.12.013]

A possible role of FANCM mutations in male breast cancer susceptibility: Results from a multicenter study in Italy

Bianchi, Simonetta;
2018

Abstract

Introduction: Breast cancer (BC) in men is a rare disease, whose etiology appears to be associated with genetic factors. Inherited mutations in BRCA1/2 genes account for about 10e15% of all cases. FANCM, functionally linked to BRCA1/2, has been suggested as a novel BC susceptibility gene. Our aim was to test if FANCM germline mutations could further explain male BC (MBC) susceptibility. Methods: We screened the entire coding region of FANCM in 286 MBCs by a multi-gene panel analysis, and compared these data with available whole exome sequencing data from 415 men used as population controls. Moreover, we genotyped the two most frequent FANCM mutations (c.5101C>T and c.5791C>T) in 506 MBCs and 854 healthy male controls. Results: Two FANCM truncating mutations, the c.1432C>T (p.Arg478Ter) and c.1972C>T (p.Arg658Ter), were identified in two MBC cases (0.7%). When specifically considering cases at increased genetic risk for BC, FANCM mutation frequency raises up to 1%. One mutation, the c.2201_2202delCT (p.Ser734Terfs), was found among controls (0.24%). Mutation frequency in cases was higher than in controls, however this difference was not statistically significant. FANCM c.5101C>T was not present in any of the cases and controls analyzed, whereas FANCM c.5791C>T was found in two controls (0.23%). Conclusion: Rare FANCM truncating mutations, other than c.5101C>T and c.5791C>T, may have a role in MBC susceptibility. The inclusion of FANCM in gene panels for research purpose would allow for the identification of a higher number of mutation carriers, thus helping estimate BC risk associated with FANCM mutations.
2018
38
92
97
Silvestri, Valentina; Rizzolo, Piera; Zelli, Veronica; Valentini, Virginia; Zanna, Ines; Bianchi, Simonetta; Tibiletti, Maria Grazia; Varesco, Liliana...espandi
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1149577
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