Identification of candidate cancer predisposing variants by performing whole-exome sequencing on index patients from BRCA1 and BRCA2-negative breast cancer families.

Background: In the majority of familial breast cancer (BC) families, the etiology of the disease remains unresolved. To identify missing BC heritability resulting from relatively rare variants (minor allele frequency ≤ 1%), we have performed whole exome sequencing followed by variant analysis in a virtual panel of 492 cancer-associated genes on BC patients from BRCA1 and BRCA2 negative families with elevated BC risk.

Methods: BC patients from 54 BRCA1 and BRCA2-negative families with elevated BC risk and 120 matched controls were considered for germline DNA whole exome sequencing.

The impact of an interventional counselling procedure in families with a BRCA1/2 gene mutation: efficacy and safety.

Background: Predictive genetic testing has high impact on cancer prevention for BRCA carriers and passing this information in BRCA families is important. Mostly, this is proband-mediated but this path is defective and denies relatives lifesaving information.

Objective: To assess the efficacy/safety of an intervention, in which relatives are actively informed.