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

Valentina Silvestri, Piera Rizzolo, Veronica Zelli, Virginia Valentini, Ines Zanna, Simonetta Bianchi, Maria Grazia Tibiletti, Liliana Varesco, Antonio Russo, Stefania Tommasi, Anna Coppa, Carlo Capalbo, Daniele Calistri, Alessandra Viel, Laura Cortesi, Siranoush Manoukian, Bernardo Bonanni, Marco Montagna, Domenico Palli, Paolo RadicePaolo Peterlongo, Laura Ottini

Research output: Contribution to journalArticlepeer-review


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 10-15% 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.

Original languageEnglish
Pages (from-to)92-97
Number of pages6
Early online dateDec 26 2017
Publication statusPublished - Apr 2018


  • Journal Article


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