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.
PATIENTS AND 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.