Mutation screening of PALB2 in clinically ascertained families from the Breast Cancer Family Registry.

摘要: Loss-of-function mutations in PALB2 are associated with an increased risk of breast cancer, recent data showing that female cancer risks for mutation carriers comparable magnitude to those BRCA2 carriers. This study applied targeted massively parallel sequencing characterize the spectrum probands attending genetics clinics USA. The coding regions and proximal intron–exon junctions were screened not known carry a BRCA1 or BCRA2 from 1,250 families enrolled through familial by Breast Cancer Family Registry. Mutation screening was performed using Hi-Plex, amplicon-based platform. Screening successful 1,240/1,250 identified nine women protein-truncating (three nonsense five frameshift mutations). Four 33 missense variants predicted be deleterious protein function silico analysis two different programs. Analysis tumors truncating revealed majority high histological grade, invasive ductal carcinomas. Young onset apparent most families, 19 cancers under 50 years age, including eight age 40 years. Our demonstrate utility Hi-Plex context high-throughput testing rare genetic provide additional timely information about nature prevalence mutations, enhance assessment management at clinical services.