title: Further evidence for germline BAP1 mutations predisposing to melanoma and malignant mesothelioma.
abstract: We describe a new family with a novel germline BAP1 nonsense mutation, c.723T>G, which leads to a predicted truncated protein, p.Y241*, or nonsense-mediated decay of the BAP1 mRNA. The proband had uveal melanoma (UM), and his paternal family has a remarkable history of multiple cancers. The proband's father had both pleural malignant mesothelioma (MM) and cutaneous melanoma (CM); a paternal uncle had lung cancer, CM, and UM; and a grandmother had CM. The findings in this family provide further support for the existence of a BAP1 cancer syndrome that predisposes to MM, various melanocytic neoplasms, and potentially other cancers. The fact that several members of the family manifested two or more different types of cancer suggests widespread BAP1-related tumor susceptibility targeting tissues of multiple organs. In addition, a review of BAP1 cancer syndrome families reported to date indicates that the location of the BAP1 mutation does not have any bearing on the spectrum of cancer types observed, either for mesothelial or melanocytic tumors.
authors.affiliation: Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA, USA.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Cheung
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Talarchek
authors.forename: Karen
authors.initials: K
authors.lastname: Schindeler
authors.forename: Eduardo
authors.initials: E
authors.lastname: Saraiva
authors.forename: Lynette S
authors.initials: LS
authors.lastname: Penney
authors.forename: Mark
authors.initials: M
authors.lastname: Ludman
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Testa
mesh_terms: D018389:Codon, Nonsense; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008654:Mesothelioma / Q000235:genetics*; D000086002:Mesothelioma, Malignant; D010375:Pedigree; D020871:RNA Stability / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D043222:Ubiquitin Thiolesterase / Q000235:genetics*
chemical_list: C400134:BAP1 protein, human; D018389:Codon, Nonsense; D025521:Tumor Suppressor Proteins; D043222:Ubiquitin Thiolesterase
keywords: BAP1; cancer susceptibility; cutaneous melanoma; mesothelioma; uveal melanoma