Genome Sequencing of Multiple Primary Tumors Reveals a Novel PALB2 Variant (BRCA1/2/Ashkenazi Jewish...)

Genome Sequencing of Multiple Primary Tumors Reveals a Novel PALB2 Variant
 

Discussion

We performed WGS of multiple primary cancers and identified a novel germline PALB2 structural variant responsible for inherited susceptibility to ovarian serous adenocarcinoma and mammary invasive ductal carcinoma. The finding of a germline mutation in PALB2 has implications for the patient and her family.....

.... Apart from BRCA1/2, the basis for genetic susceptibility to breast and ovarian cancer is heterogeneous, requiring sequential or multiplex testing. Panels directed towards breast and ovarian cancer susceptibility include genes like ATM, BRIP1, and PALB2.¹⁹ While this PALB2 deletion might have been detected using a panel approach, such methods are not designed to scan the entire genome. Although successful in diagnosing the underlying genetic susceptibility in up to 30% of BRCA1/2-negative familial breast cancer cases,^19,20 panels are limited by the current state of knowledge of known or presumed cancer susceptibility genes, whereas the approach demonstrated here could potentially uncover changes in novel susceptibility genes....