The Spectrum of FANCM Protein Truncating Variants in European Breast Cancer Cases

Abstract

Germline protein truncating variants (PTVs) in the <i>FANCM</i> gene have been associated with a 2-4-fold increased breast cancer risk in case-control studies conducted in different European populations. However, the distribution and the frequency of <i>FANCM</i> PTVs in Europe have never been investigated. In the present study, we collected the data of 114 European female breast cancer cases with <i>FANCM</i> PTVs ascertained in 20 centers from 13 European countries. We identified 27 different <i>FANCM</i> PTVs. The p.Gln1701* PTV is the most common PTV in Northern Europe with a maximum frequency in Finland and a lower relative frequency in Southern Europe. On the contrary, p.Arg1931* seems to be the most common PTV in Southern Europe. We also showed that p.Arg658*, the third most common PTV, is more frequent in Central Europe, and p.Gln498Thrfs*7 is probably a founder variant from Lithuania. Of the 23 rare or unique <i>FANCM</i> PTVs, 15 have not been previously reported. We provide here the initial spectrum of <i>FANCM</i> PTVs in European breast cancer cases.