フルカワ　トオル   Furukawa Tooru   古川　徹    所属   医学部 医学科（東京女子医科大学病院）    職種   客員教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Whole exome sequencing reveals recurrent mutations in BRCA2 and FAT genes in acinar cell carcinomas of the pancreas.
掲載誌名	正式名：Scientific Reports 略　 称：Sci Rep ISSNコード：20452322
巻・号・頁	5,pp.8829
著者・共著者	FURUKAWA Toru†*, SAKAMOTO Hitomi, TAKEUCHI Shoko, AMERI Mitra, KUBOKI Yuko, YAMAMOTO Toshiyuki, HATORI Takashi, YAMAMOTO Masakazu, SUGIYAMA Masanori, OHIKE Noriyuki, YAMAGUCHI Hiroshi, SHIMIZU Michio, SHIBATA Noriyuki, SHIMIZU Kyoko, SHIRATORI Keiko
担当区分	筆頭著者,責任著者
発行年月	2015/03
概要	Acinar cell carcinoma of the pancreas is a rare tumor with a poor prognosis. Compared to pancreatic ductal adenocarcinoma, its molecular features are poorly known. We studied a total of 11 acinar cell carcinomas, including 3 by exome and 4 by target sequencing. Exome sequencing revealed 65 nonsynonymous mutations and 22 indels with a mutation rate of 3.4 mutations/Mb per tumor, on average. By accounting for not only somatic but also germline mutations with loss of the wild-type allele, we identified recurrent mutations of BRCA2 and FAT genes. BRCA2 showed somatic or germline premature termination mutations, with loss of the wild-type allele in 3 of 7 tumors. FAT1, FAT3, and FAT4 showed somatic or germline missense mutations in 4 of 7 tumors. The germline FAT mutations were with loss of the wild-type allele. Loss of BRCA2 expression was observed in 5 of 11 tumors. One patient with a BRCA2-mutated tumor experienced complete remission of liver metastasis following cisplatinum chemotherapy. In conclusion, acinar cell carcinomas show a distinct mutation pattern and often harbor somatic or germline mutations of BRCA2 and FAT genes. This result may warrant assessment of BRCA2 abrogation in patients with the carcinoma to determine their sensitivity to chemotherapy.
DOI	10.1038/srep08829
PMID	25743105