title: Germline mutations in BAP1 predispose to melanocytic tumors.
abstract: Common acquired melanocytic nevi are benign neoplasms that are composed of small, uniform melanocytes and are typically present as flat or slightly elevated pigmented lesions on the skin. We describe two families with a new autosomal dominant syndrome characterized by multiple, skin-colored, elevated melanocytic tumors. In contrast to common acquired nevi, the melanocytic neoplasms in affected family members ranged histopathologically from epithelioid nevi to atypical melanocytic proliferations that showed overlapping features with melanoma. Some affected individuals developed uveal or cutaneous melanomas. Segregating with this phenotype, we found inactivating germline mutations of BAP1, which encodes a ubiquitin carboxy-terminal hydrolase. The majority of melanocytic neoplasms lost the remaining wild-type allele of BAP1 by various somatic alterations. In addition, we found BAP1 mutations in a subset of sporadic melanocytic neoplasms showing histological similarities to the familial tumors. These findings suggest that loss of BAP1 is associated with a clinically and morphologically distinct type of melanocytic neoplasm.
authors.affiliation: Department of Dermatology, Medical University of Graz, Graz, Austria. wiesnert@mskcc.org
authors.forename: Thomas
authors.initials: T
authors.lastname: Wiesner
authors.forename: Anna C
authors.initials: AC
authors.lastname: Obenauf
authors.forename: Rajmohan
authors.initials: R
authors.lastname: Murali
authors.forename: Isabella
authors.initials: I
authors.lastname: Fried
authors.forename: Klaus G
authors.initials: KG
authors.lastname: Griewank
authors.forename: Peter
authors.initials: P
authors.lastname: Ulz
authors.forename: Christian
authors.initials: C
authors.lastname: Windpassinger
authors.forename: Werner
authors.initials: W
authors.lastname: Wackernagel
authors.forename: Shea
authors.initials: S
authors.lastname: Loy
authors.forename: Ingrid
authors.initials: I
authors.lastname: Wolf
authors.forename: Agnes
authors.initials: A
authors.lastname: Viale
authors.forename: Alex E
authors.initials: AE
authors.lastname: Lash
authors.forename: Mono
authors.initials: M
authors.lastname: Pirun
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Socci
authors.forename: Arno
authors.initials: A
authors.lastname: Rütten
authors.forename: Gabriele
authors.initials: G
authors.lastname: Palmedo
authors.forename: David
authors.initials: D
authors.lastname: Abramson
authors.forename: Kenneth
authors.initials: K
authors.lastname: Offit
authors.forename: Arthur
authors.initials: A
authors.lastname: Ott
authors.forename: Jürgen C
authors.initials: JC
authors.lastname: Becker
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Cerroni
authors.forename: Heinz
authors.initials: H
authors.lastname: Kutzner
authors.forename: Boris C
authors.initials: BC
authors.lastname: Bastian
authors.forename: Michael R
authors.initials: MR
authors.lastname: Speicher
mesh_terms: D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D009508:Nevus, Pigmented / Q000235:genetics*; D010375:Pedigree; D012878:Skin Neoplasms / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000235:genetics* / Q000378:metabolism
chemical_list: C400134:BAP1 protein, human; D025521:Tumor Suppressor Proteins; D043222:Ubiquitin Thiolesterase