A BAP1 mutation in a Danish family predisposes to uveal melanoma and other cancers

• Published in: PloS one 2013-08, Vol.8 (8), p.e72144-e72144
• Main Authors: Aoude, Lauren G, Wadt, Karin, Bojesen, Anders, Crüger, Dorthe, Borg, Ake, Trent, Jeffrey M, Brown, Kevin M, Gerdes, Anne-Marie, Jönsson, Göran, Hayward, Nicholas K
• Format: Article
• Language: English
• Subjects: Adult; Age; Aged; Amino Acid Sequence; Base Sequence; Bioinformatics; Biology; BRCA1 protein; Breast cancer; Cancer; Cancer and Oncology; Cancer och onkologi; Case-Control Studies; Clinical Medicine; Denmark; Development and progression; DNA Mutational Analysis; Family; Female; Frameshift Mutation; Gastric cancer; Gene mutation; Genetic aspects; Genetic Association Studies; Genetic Predisposition to Disease; Genomics; Humans; Klinisk medicin; Laboratories; Lesions; Loss of Heterozygosity; Lung cancer; Male; Medical and Health Sciences; Medical research; Medicin och hälsovetenskap; Medicine; Melanoma; Melanoma - enzymology; Melanoma - genetics; Mesothelioma; Metastasis; Middle Aged; Molecular Sequence Data; Mutation; Pedigree; Protein Isoforms - genetics; Proteins; RNA Splice Sites; Siblings; Skin; Skin cancer; Skin diseases; Stomach; Tumor suppressor genes; Tumor Suppressor Proteins - genetics; Tumors; Ubiquitin Thiolesterase - genetics; Uveal Neoplasms - enzymology; Uveal Neoplasms - genetics; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0072144

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.