Germline mutations in BAP1 predispose to melanocytic tumors Journal Article
| Authors: | Wiesner, T.; Obenauf, A. C.; Murali, R.; Fried, I.; Griewank, K. G.; Ulz, P.; Windpassinger, C.; Wackernagel, W.; Loy, S.; Wolf, I.; Viale, A.; Lash, A. E.; Pirun, M.; Socci, N. D.; Rütten, A.; Palmedo, G.; Abramson, D.; Offit, K.; Ott, A.; Becker, J. C.; Cerroni, L.; Kutzner, H.; Bastian, B. C.; Speicher, M. R. |
| Article 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. © 2011 Nature America, Inc. All rights reserved. |
| Keywords: | clinical article; controlled study; unclassified drug; somatic mutation; histopathology; cell proliferation; phenotype; cancer susceptibility; melanoma; skin neoplasms; melanocyte; wild type; pedigree; skin tumor; melanocytic nevus; nevus, pigmented; nucleotide sequence; tumor suppressor proteins; tumor protein; gene loss; familial cancer; uvea melanoma; genetic predisposition; autosomal dominant disorder; germ-line mutation; ubiquitin thiolesterase; bap1 protein |
| Journal Title: | Nature Genetics |
| Volume: | 43 |
| Issue: | 10 |
| ISSN: | 1061-4036 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2011-08-28 |
| Start Page: | 1018 |
| End Page: | 1022 |
| Language: | English |
| DOI: | 10.1038/ng.910 |
| PROVIDER: | scopus |
| PUBMED: | 21874003 |
| PMCID: | PMC3328403 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 2 November 2011" - "CODEN: NGENE" - "Source: Scopus" |
