Multiplex testing in high risk BRCA1/2-negative families.

e12557 Background: Familial breast cancer is a heterogeneous genetic condition. Susceptibility cancer gene panels that allow simultaneous analysis of multiple genes might broaden genetic diagnosis compared to sequential single testing. Methods: Two-hundred BRCA1/2-negative patients from high risk families were enrolled in a research study for massive parallel sequencing of 98 cancer susceptibility genes. We report preliminary results of the first 39 patients while the study is still ongoing. The inclusion criteria were (1) breast cancer (BC) under age 35, (2) presence of ovarian cancer under the age 50 in the family or (3) at least 3 breast or ovarian cancers under age 60 years in the family. DNA samples were processed using Agilent’s SureSelect Target Enrichment and sequenced on an Illumina MiSeq (2x150). The bioinformatic pipeline includes read alignment, variant calling by GATK and VarScan2, and annotation with ANNOVAR and ALAMUT. Results: Twelve truncating mutations were identified in PALB2 (2), ATM (...