Identification of susceptible genes in familial pancreatic cancer in Japan

2014 Fiscal Year Final Research Report

• Project/Area Number: 24390090
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: FURUKAWA Toru 東京女子医科大学, 医学部, 教授 (30282122)
• Co-Investigator(Kenkyū-buntansha): SHIMIZU Kyoko 東京女子医科大学, 医学部, 准教授 (90187451)
• Co-Investigator(Renkei-kenkyūsha): FURUSE Junji 杏林大学, 医学部, 教授 (10501869) ; SUGIYAMA Masanori 杏林大学, 医学部, 教授 (20192825) ; YAMAMOTO Masakazu 東京女子医科大学, 医学部, 教授 (60220498)
• Research Collaborator: SAITO Kayoko 東京女子医科大学, 医学部, 教授 (90138834) ; KAMATANI Naoyuki 東京女子医科大学, 医学部, 客員教授 (00114447)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 膵臓がん / 家族性腫瘍 / 全エクソン解析 / 次世代シーケンサー / 遺伝子 / DNA解析 / SNP / 人類遺伝

Outline of Final Research Achievements

We examined 47 individuals in 22 families of Japanese familial pancreatic cancer kindred to identify susceptible germline variants by whole exome sequencing. Nonsynonymous single nucleotide variants, splice-site variants, insertions, and deletions that were rarely found or not found in the 1000 Genome or the Human Genetic Variation databases were collected. Known susceptible genes and genes identified as candidate pancreatic cancer genes in the mouse sleeping beauty experiment were selected. We found potentially susceptible germline variants in BRCA2, PALB2, PUM1, FARP1, FAM193A, CTNNA1, and MLL5. These germline variants may contribute to susceptibility to familial pancreatic cancer in Japan. We also examined acinar cell carcinoma cases by whole exome and found germline variants in BRCA2 and FAT genes with loss of the wild type allele in cancer tissues. Moreover, we determined clinicopathological and molecular characteristics of familial pancreatic cancer and its associated lesions.

Free Research Field

人体病理学