094 BUB1B germline variant predisposes to cutaneous melanoma and multiple other primary malignancies

Although several inherited melanoma predisposition syndromes have been identified, a subset of families lack pathogenic variants in known highly penetrant genes, including CDKN2A, CDK4, and BAP1. We describe patient with multiple melanomas other primary tumors germline variant BUB1B. A 76-year-old woman presented history multiple, distinct tumors, childhood thymoma, thyroid cancer, two melanomas, breast cancers, solitary fibrous tumor, metastasized lung cancer. Family included brothers prostate cancer cutaneous melanoma, maternal relatives colon father urinary tract Germline testing 75 risk hereditary additional whole-exome sequencing (WES) revealed only one variant, c.2316C>G, WES somatic variants, CDKN2A NRAS.Immunohistochemistry BUB1B normal skin, nevus, samples did not reveal significant differences expression levels versus control tissues. encodes kinase involved spindle checkpoint function, process dysregulated many types. To date, rarely implicated tumor predisposition. propose that heterozygous may increase susceptibility to explain this patient’s cancers. Identification novel genes associated is integral for optimal genetic counseling appropriate screening at-risk individuals.