title: A BAP1 mutation in a Danish family predisposes to uveal melanoma and other cancers.
abstract: Truncating germline mutations in the tumor suppressor gene BRCA-1 associated protein-1 (BAP1) have been reported in families predisposed to developing a wide range of different cancer types including uveal melanoma and cutaneous melanoma. There has also been an association between amelanotic tumor development and germline BAP1 mutation suggesting a possible phenotypic characteristic of BAP1 mutation carriers. Though there have been many types of cancer associated with germline BAP1 mutation, the full spectrum of disease association is yet to be ascertained. Here we describe a Danish family with predominantly uveal melanoma but also a range of other tumor types including lung, neuroendocrine, stomach, and breast cancer; as well as pigmented skin lesions. Whole-exome sequencing identified a BAP1 splice mutation located at c.581-2A>G, which leads to a premature truncation of BAP1 in an individual with uveal melanoma. This mutation was carried by several other family members with melanoma or various cancers. The finding expands on the growing profile of BAP1 as an important uveal and cutaneous melanoma tumor suppressor gene and implicates its involvement in the development of lung, and stomach cancer.
authors: Oncogenomics Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland, Australia ; University of Queensland, Brisbane, Queensland, Australia.
authors: Lauren G
authors: LG
authors: Aoude
authors: Karin
authors: K
authors: Wadt
authors: Anders
authors: A
authors: Bojesen
authors: Dorthe
authors: D
authors: Crüger
authors: Ake
authors: A
authors: Borg
authors: Jeffrey M
authors: JM
authors: Trent
authors: Kevin M
authors: KM
authors: Brown
authors: Anne-Marie
authors: AM
authors: Gerdes
authors: Göran
authors: G
authors: Jönsson
authors: Nicholas K
authors: NK
authors: Hayward
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D003718:Denmark; D005260:Female; D016368:Frameshift Mutation; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008545:Melanoma / Q000201:enzymology / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D020033:Protein Isoforms / Q000235:genetics; D022821:RNA Splice Sites; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D043222:Ubiquitin Thiolesterase / Q000235:genetics*; D014604:Uveal Neoplasms / Q000201:enzymology / Q000235:genetics*; D055815:Young Adult; D000098943:Uveal Melanoma
chemical_list: C400134:BAP1 protein, human; D020033:Protein Isoforms; D022821:RNA Splice Sites; D025521:Tumor Suppressor Proteins; D043222:Ubiquitin Thiolesterase
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