Multilocus Inherited Neoplasia Alleles Syndrome: A Retrospective Review from a Canadian Single Institution

Genetic testing in hereditary cancer is evolving from single-gene focused approaches on affected individuals to multi-gene panel testing in affected individuals and unaffected relatives. The widespread use of multi-gene panel testing has led to the identification of individuals with two or more pathogenic or likely pathogenic variants in hereditary cancer susceptibility genes (CSGs), termed Multilocus Inherited Neoplasia Allele Syndrome (MINAS) carriers. It remains unclear whether MINAS carriers are at increased risk of multiple, atypical or more severe cancer phenotypes, and currently, there is no consensus on how best to identify and manage cancer risk. In this retrospective study, we identified 54 MINAS carriers at Princess Margaret Cancer Centre in Toronto, Canada. The majority of affected MINAS carriers had a cancer consistent with expression of at least one pathogenic variant, although nearly 40% were diagnosed with at least one cancer outside of the typical spectrum of their CSGs. The most frequent gene pair combinations included hereditary breast cancer genes, with some carriers exhibiting earlier age of breast cancer onset than single CSG variants reported in the literature. Overall, our study indicates that the cancer spectrum associated with certain CSGs is expanding and suggests more intensive cancer surveillance for subgroups of MINAS carriers with hereditary breast cancer CSGs.