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

Autor: Yoshio Miki, Yuri Sato, Sachio Nomura, Eri Nakashima, Shinji Ohno, Masami Arai, Reiko Yoshida, Mizuho Kita, Takuji Iwase, Yasue Adachi, Yuumi Ashihara, Dai Kitagawa, Katsutoshi Sato, Mio Koyasu
Rok vydání: 2017
Předmět:
Zdroj: Cancer Science. 108:2287-2294
ISSN: 1349-7006
1347-9032
DOI: 10.1111/cas.13350
Popis: In addition to BRCA1 and BRCA2, RAD51C, PALB2 and BRIP1 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 RAD51C, PALB2 and BRIP1 in 100 Japanese patients diagnosed with familial breast and ovarian cancer and without BRCA1 and BRCA2 mutations. We detected a large deletion from exons 6 to 9 in RAD51C, 4 novel BRIP1 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 PALB2 was detected. The results of pedigree analysis showed that the proband with a large deletion on RAD51C had a family history of both breast and ovarian cancer, and the families of probands with novel BRIP1 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 RAD51C in Japanese familial breast cancer cases was similar to that in Western countries and that the prevalence of deleterious mutation of PALB2 was possibly lower. Furthermore, our results suggested that BRIP1 mutation frequency in Japan might differ from that in Western countries.
Databáze: OpenAIRE
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