Mutation status of RAD 51C , PALB 2 and BRIP 1 in 100 Japanese familial breast cancer cases without BRCA 1 and BRCA 2 mutations

In addition to BRCA 1 and BRCA 2, RAD 51C , PALB 2 and BRIP 1 are known as breast cancer susceptibility genes. However, the mutation status of these genes in Japanese familial breast cancer cases has not yet been evaluated. To this end, we analyzed the exon sequence and genomic rearrangement of RAD 51C , PALB 2 and BRIP 1 in 100 Japanese patients diagnosed with familial breast and ovarian cancer and without BRCA 1 and BRCA 2 mutations. We detected a large deletion from exons 6 to 9 in RAD 51C , 4 novel BRIP 1 missense variants containing 3 novel non‐synonymous variants, c.89A>C, c.736A>G and c.2131A>G, and a splice donor site variant c.918+2T>C. No deleterious variant of PALB 2 was detected. The results of pedigree analysis showed that the proband with a large deletion on RAD 51C had a family history of both breast and ovarian cancer, and the families of probands with novel BRIP 1 missense variants included a male patient with breast cancer or many patients with breast cancer within the second‐degree relatives. We showed that the mutation frequency of RAD 51C in Japanese familial breast cancer cases was similar to that in Western countries and that the prevalence of deleterious mutation of PALB 2 was possibly lower. Furthermore, our results suggested that BRIP 1 mutation frequency in Japan might differ from that in Western countries.