Germline BAP1 Inactivation Is Preferentially Associated with Metastatic Ocular Melanoma and Cutaneous-Ocular Melanoma Families

摘要: Background BAP1 has been shown to be a target of both somatic alteration in high-risk ocular melanomas (OM) and germline inactivation few individuals from cancer-prone families. These findings suggest that constitutional BAP1 changes may predispose metastatic OM familial permeation deleterious alleles could delineate new cancer syndrome. Design To characterize BAP1's contribution melanoma risk, we sequenced set 100 patients with OM, including 50 cases matched non-metastatic controls, 200 cutaneous (CM) 7 CM CM-OM families 193 CM-non-OM kindreds. Results Germline mutations were detected 4/50 0/50 (8% vs. 0%, p = 0.059). Since 2/4 the carriers reported family history CM, analyzed additional hereditary found 2/7 probands 1/193 kindreds (29% 0.52%, .003). Germline co-segregated phenotypes associated presence unique nevoid highly atypical melanoma-like melanocytic proliferations (NEMMPs). Interestingly, 7/14 variants identified date reside C-terminus suggesting BRCA1 binding domain is important predisposition. Conclusion are more aggressive phenotype recurrent phenotypic complex cutaneous/ocular melanoma, other internal neoplasms (ie. COMMON syndrome), which useful clinical marker for constitutive inactivation.