title: Analysis of PALB2 mutations in 155 Japanese patients with breast and/or ovarian cancer.
abstract: BACKGROUND
  PALB2 (Partner and Localizer of BRCA2) was identified as a moderate-risk gene in breast and pancreatic cancers. Recently, it was reported that PALB2 carriers have a high risk of developing breast cancer, with the cumulative risk of 34 % by the age of 70.
  
  
  METHODS
  Peripheral blood samples from 155 patients at risk for hereditary breast and/or ovarian cancer were tested for BRCA1/2 and PALB2 by targeted sequencing using a next-generation sequencer. Of these 155, 146 met NCCN criteria and the remaining 9 did not.
  
  
  RESULTS
  BRCA1/2 analysis was performed on 155 patients, for whom the results were reported previously (Hirotsu Y et al. Mol Genet Genomic Med, doi:10.1002/mgg3.157, 2015). Eleven patients were identified to have deleterious BRCA mutations (Hirotsu Y et al. Mol Genet Genomic Med, doi:10.1002/mgg3.157, 2015). However, none of the 155 patients were found to have deleterious PALB2 germline mutations. Missense mutations [variants of uncertain significance (VUS)] of PALB2 were found in 12 cases. In silico analyses by SIFT (Sorting Intolerant Form Tolerant) and PolyPhen2 (Polymorphism Phenotyping version 2) indicated that 2 of 12 VUS were deleterious and probably damaging.
  
  
  CONCLUSIONS
  This is the first report on PALB2 mutations in Japan, revealing two missense mutations as "deleterious and probably damaging" by in silico analyses, but no PALB2 premature truncation mutations were identified. The sample size is relatively small and a larger cohort study is needed in Japan.
authors.affiliation: Department of Breast Surgery, Yamanashi Prefectural Central Hospital, 1-1-1 Fujimi, Kofu, 400-0027, Japan. h-nakagomi@ych.pref.yamanashi.jp.|Department of Surgery, Yamanashi Prefectural Central Hospital, 1-1-1 Fujimi, Kofu, 400-0027, Japan. h-nakagomi@ych.pref.yamanashi.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakagomi
authors.affiliation: Department of Gynecology, Yamanashi Prefectural Central Hospital, 1-1-1 Fujimi, Kofu, 400-0027, Japan.
authors.forename: Ikuko
authors.initials: I
authors.lastname: Sakamoto
authors.affiliation: Genome Analysis Center, Yamanashi Prefectural Central Hospital, 1-1-1 Fujimi, Kofu, 400-0027, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Hirotsu
authors.affiliation: Genome Analysis Center, Yamanashi Prefectural Central Hospital, 1-1-1 Fujimi, Kofu, 400-0027, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Amemiya
authors.affiliation: Genome Analysis Center, Yamanashi Prefectural Central Hospital, 1-1-1 Fujimi, Kofu, 400-0027, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Mochiduki
authors.affiliation: Genome Analysis Center, Yamanashi Prefectural Central Hospital, 1-1-1 Fujimi, Kofu, 400-0027, Japan.|University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo, 113-8654, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Omata
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D015331:Cohort Studies; D000076164:Fanconi Anemia Complementation Group N Protein; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007564:Japan; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D010375:Pedigree; D011379:Prognosis; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D000076164:Fanconi Anemia Complementation Group N Protein; D009687:Nuclear Proteins; C512790:PALB2 protein, human; D025521:Tumor Suppressor Proteins
keywords: Breast cancer; Japanese; Ovarian cancer; PALB2 mutation