title: Germline BAP1 mutation predisposes to uveal melanoma, lung adenocarcinoma, meningioma, and other cancers.
abstract: OBJECTIVE
  To investigate the potential contribution of germline sequence alterations in the BAP1 gene in uveal melanoma (UM) patients with possible predisposition to hereditary cancer.
  
  
  METHODS
  A total of 53 unrelated UM patients with high risk for hereditary cancer and five additional family members of one proband were studied. Mutational screening was carried out by direct sequencing.
  
  
  RESULTS
  Of the 53 UM patients studied, a single patient was identified with a germline BAP1 truncating mutation, c. 799 C→T (p.Q267X), which segregated in several family members and was associated with UM and other cancers. Biallelic inactivation of BAP1 and decreased BAP1 expression were identified in the UM, lung adenocarcinoma and meningioma tumours from three family members with this germline BAP1 mutation. Germline BAP1 variants of uncertain significance, likely non-pathogenic, were also identified in two additional UM patients.
  
  
  CONCLUSIONS
  This study reports a novel hereditary cancer syndrome caused by a germline BAP1 mutation that predisposes patients to UM, lung carcinoma, meningioma, and possibly other cancers. The results indicate that BAP1 is the candidate gene in only a small subset of hereditary UM, suggesting the contribution of other candidate genes.
authors.affiliation: Department of Ophthalmology, The Ohio State University, Columbus, Ohio, USA. mohamed.abdel-rahman@osumc.edu
authors.forename: Mohamed H
authors.initials: MH
authors.lastname: Abdel-Rahman
authors.forename: Robert
authors.initials: R
authors.lastname: Pilarski
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Cebulla
authors.forename: James B
authors.initials: JB
authors.lastname: Massengill
authors.forename: Benjamin N
authors.initials: BN
authors.lastname: Christopher
authors.forename: Getachew
authors.initials: G
authors.lastname: Boru
authors.forename: Peter
authors.initials: P
authors.lastname: Hovland
authors.forename: Frederick H
authors.initials: FH
authors.lastname: Davidorf
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D030342:Genetic Diseases, Inborn / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006801:Humans; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008577:Meningeal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008579:Meningioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018895:Microsatellite Repeats; D008875:Middle Aged; D010375:Pedigree; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000235:genetics* / Q000378:metabolism; D014604:Uveal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000098943:Uveal Melanoma
chemical_list: C400134:BAP1 protein, human; D025521:Tumor Suppressor Proteins; D043222:Ubiquitin Thiolesterase