Mutation spectra of the
BRCA1
/
2
genes in human breast and ovarian cancer and germline
Abstract
Annotating genomic sequence alterations is sometimes a difficult decision, particularly in missense variants with uncertain pathogenic significance and also in those presumed as germline pathogenic variants. We here suggest that mutation spectrum may also be useful for judging them. From the public databases, 982
BRCA1
/1861
BRCA2
germline missense variants and 294
BRCA1
/420
BRCA2
somatic missense variants were obtained. We then compared their mutation spectra, i.e., the frequencies of two transition‐ and four transversion‐type mutations, in each category. Intriguingly, in
BRCA1
variants, A:T to C:G transversion, which was relatively frequent in the germline, was extremely rare in somatic, particularly breast cancer, cells (
p
= .03). Conversely, A:T to T:A transversion was most infrequent in the germline, but not rare in somatic cells. Thus,
BRCA1
variants with A:T to T:A transversion may be suspected as somatic, and those with A:T to C:G as being in the germline. These tendencies of mutation spectrum may also suggest the biological and chemical origins of the base alterations. On the other hand, unfortunately, variants of uncertain significance (VUS) were not distinguishable by mutation spectrum. Our findings warrant further and more detailed studies.
