3p21.31-p21.2 HGNC:950 MIM.603089
Thursday 15 March 2012
BRCA1-associated protein-1 (ubiquitin carboxy-terminal hydrolase) hucep-6, KIAA0272, UCHL2
Germline mutations in BAP1
- Germline mutations in BAP1 cause a familial tumor syndrome characterized by high penetrance for melanocytic tumors with distinct clinical and histologic features.
- Melanocytic neoplasms in affected individuals harbored BRAF mutations, showed loss of BAP1 expression, and histologically resembled so-called "atypical Spitz tumors" (ASTs).
- BRAF-mutated, BAP1-negative tumors are primarily located in the dermis and are composed entirely or predominantly of epithelioid melanocytes with abundant amphophilic cytoplasm and well-defined cytoplasmic borders.
- Nuclei are commonly vesicular and exhibited substantial pleomorphism and conspicuous nucleoli.
- The combination of BRAF mutation and loss of nuclear BAP1 expression thus characterizes a subset of "atypical Spitz tumors" (ASTs) with distinct histologic features.
- - BAP1-mutated clear cell renal cell carcinoma
BAP1 is mutated in clear cell renal cell carcinoma
- BAP1 is mutated in about 15% of clear-cell renal-cell carcinoma.
- BAP1 and PBRM1 mutations are largely mutually exclusive.
- BAP1 and PBRM1 mutation-defined subtypes of clear-cell renal-cell carcinoma with distinct clinical outcomes, a high-risk BAP1-mutant group and a favourable PBRM1-mutant group.
- The molecular genetic classification of clear-cell renal-cell carcinoma could influence treatment decisions in the future.
- The existence of different molecular subtypes with disparate outcomes should be considered in the design and assessment of clinical studies.
Effects on survival of BAP1 and PBRM1 mutations in sporadic clear-cell renal-cell carcinoma: a retrospective analysis with independent validation. Payal Kapur et al. The Lancet Oncology, Early Online Publication, 16 January 2013. doi : 10 1016/S1470-2045(12)70584-3
A Distinct Subset of Atypical Spitz Tumors is Characterized by BRAF Mutation and Loss of BAP1 Expression. Wiesner T, Murali R, Fried I, Cerroni L, Busam K, Kutzner H, Bastian BC. Am J Surg Pathol. 2012 Feb 24. PMID: 22367297