Contribution of large genomic rearrangements in PALB2 to familial breast cancer: Implications for genetic testing

Abstract

Background PALB2 is the most important contributor to familial breast cancer after BRCA1 and BRCA2. Large genomic rearrangements (LGRs) in BRCA1 and BRCA2 are routinely assessed in clinical testing and are a significant contributor to the yield of actionable findings. In contrast, the contribution of LGRs in PALB2 has not been systematically studied. Methods We performed targeted sequencing and real-Time qPCR validation to identify LGRs in PALB2 in 5770 unrelated patients with familial breast cancer and 5741 cancer-free control women from the same Australian population. Results Seven large deletions ranging in size from 0.96 kbp to 18.07 kbp involving PALB2 were identified in seven cases, wh..