Open AccessGermline Variants of Prostate Cancer in Japanese Families
Author(s) -
Takahide Hayano,
Hiroshi Matsui,
Hirofumi Nakaoka,
Nobuaki Ohtake,
Kazuyoshi Hosomichi,
Kazuhiro Suzuki,
Ituro Inoue
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0164233
Subject(s) - mutyh , germline , genetics , sanger sequencing , exome sequencing , prostate cancer , biology , germline mutation , cancer , exome , mlh1 , medicine , gene , colorectal cancer , dna sequencing , mutation , dna mismatch repair
Prostate cancer (PC) is the second most common cancer in men. Family history is the major risk factor for PC. Only two susceptibility genes were identified in PC, BRCA2 and HOXB13 . A comprehensive search of germline variants for patients with PC has not been reported in Japanese families. In this study, we conducted exome sequencing followed by Sanger sequencing to explore responsible germline variants in 140 Japanese patients with PC from 66 families. In addition to known susceptibility genes, BRCA2 and HOXB13 , we identified TRRAP variants in a mutually exclusive manner in seven large PC families (three or four patients per family). We also found shared variants of BRCA2 , HOXB13 , and TRRAP from 59 additional small PC families (two patients per family). We identified two deleterious HOXB13 variants (F127C and G132E). Further exploration of the shared variants in rest of the families revealed deleterious variants of the so-called cancer genes ( ATP1A1 , BRIP1 , FANCA , FGFR3 , FLT3 , HOXD11 , MUTYH , PDGFRA , SMARCA4 , and TCF3 ). The germline variant profile provides a new insight to clarify the genetic etiology and heterogeneity of PC among Japanese men.