title: Hereditary uveal melanoma: a report of a germline mutation in BAP1.
abstract: Melanoma of the eye is a rare and distinct subtype of melanoma, which only rarely are familial. However, cases of uveal melanoma (UM) have been found in families with mixed cancer syndromes. Here, we describe a comprehensive search for inherited genetic variation in a family with multiple cases of UM but no aggregation of other cancer diagnoses. The proband is a woman diagnosed with UM at 16 years who within 6 months developed liver metastases. We also identified two older paternal relatives of the proband who had died from UM. We performed exome sequencing of germline DNA from members of the affected family. Exome-wide analysis identified a novel loss-of-function mutation in the BAP1 gene, previously suggested as a tumor suppressor. The mutation segregated with the UM phenotype in this family, and we detected a loss of the wild-type allele in the UM tumor of the proband, strongly supporting a causative association with UM. Screening of BAP1 germline mutations in families predisposed for UM may be used to identify individuals at increased risk of disease. Such individuals may then be enrolled in preventive programs and regular screenings to facilitate early detection and thereby improve prognosis.
authors: Department of Oncology and Pathology, Karolinska Institutet, Karolinska University Hospital, Solna, Stockholm, Sweden. veronica.hoiom@ki.se
authors: Veronica
authors: V
authors: Höiom
authors: Daniel
authors: D
authors: Edsgärd
authors: Hildur
authors: H
authors: Helgadottir
authors: Hanna
authors: H
authors: Eriksson
authors: Charlotta
authors: C
authors: All-Ericsson
authors: Rainer
authors: R
authors: Tuominen
authors: Ivayla
authors: I
authors: Ivanova
authors: Joakim
authors: J
authors: Lundeberg
authors: Olof
authors: O
authors: Emanuelsson
authors: Johan
authors: J
authors: Hansson
mesh_terms: D000293:Adolescent; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D012307:Risk Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D043222:Ubiquitin Thiolesterase / Q000235:genetics*; D014604:Uveal Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C400134:BAP1 protein, human; D025521:Tumor Suppressor Proteins; D043222:Ubiquitin Thiolesterase