RNA profiling reveals familial aggregation of molecular subtypes in non-BRCA1/2 breast cancer families

摘要: In more than 70% of families with a strong history breast and ovarian cancers, pathogenic mutation in BRCA1 or BRCA2 cannot be identified, even though hereditary factors are expected to involved. It has been proposed that tumors similar molecular phenotypes also share underlying pathophysiological mechanisms. the current study, aim was investigate if global RNA profiling can used identify functional subgroups within from tested negative for BRCA1/2 germline mutations how these subgroupings relate different cancer patients same family. study we analyzed collection 70 frozen tumor biopsies total 58 by promoter methylation analysis. We show distinct subgroupings, intrinsic subtypes, exist among non-BRCA1/2 cancers. The distribution subtypes markedly found carriers. From 11 families, one affected family member were included study. Notably, 8 shared subtype, showing tendency familial aggregation (p-value = 1.7e-3). Using our previously developed BRCA1/2-signatures, identified 7 BRCA1-like phenotype provide evidence epigenetic inactivation three tumors. addition, BRCA2-like found. Our finding indicates involvement which members may carry genetic susceptibility not just but particular subtype cancer. This is first biological link between cancers high-risk systematic manner, suggesting future analysis benefit subgrouping into molecularly homogeneous order search new high penetrance genes.