Molecular Pathology
Melanoma mutations

Author: Joshua Bradish, M.D. (see Authors page)

Revised: 30 October 2015, last major update 6 August 2014

Copyright: (c) 2003-2015,, Inc.

PubMed Search: BAP1[title]
  • BAP1: BRCA1 Associated Protein 1, on chromosome 3p21
  • Involved in cell cycle regulation, cellular differentiation, cell death, DNA damage response (Nat Rev Cancer 2013;13:153)
  • BAP1 is a ubiquitin carboxy-terminal hydrolase (deubiquitylase)

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BAP1 interactions

Molecular / Cytogenetics Description
  • Many different types of mutations (deletions, point mutations, etc.) can lead to inactivation of BAP1 function, which is problematic for detection using molecular techniques (Pathology 2013;45:651)
  • Development of a molecular assay is difficult and laborious, due to numerous types of inactivating mutations found in BAP1
  • Currently, an immunohistochemical stain is the choice for detection of BAP1 mutations with subsequent inactivation (Pathology 2013;45:651)
Clinical Features
  • BAP1 has been associated with a cancer syndrome involving a predisposition to benign melanocytic nevi, mesothelioma, uveal melanoma and cutaneous melanoma (Nat Rev Cancer 2013;13:153)
  • Many BAP1 mutations have a concomitant BRAF mutation
  • One study found 85% of metastasizing uveal melanomas contained a BAP1 mutation (Science 2010;330:1410)
  • Lack of BAP1 expression has been associated with aggressive disease and worse survival (Pathology 2013;45:651)
  • Histone deacetylase inhibitors may be effective in uveal melanoma cell lines with a BAP1 mutation (Clin Cancer Res 2012;18:408)
Micro Description
  • Benign melanocytic nevi are often spitzoid or epitheliod
  • These melanocytic tumors may have overlapping features with melanoma
  • Spitzoid tumors often lack epidermal hyperplasia, Kamino bodies, clefting
  • Many lesions are highly cellular, pleomorphic and can contain molecular aberrations occasionally identified in melanoma (Nat Genet 2011;43:1018)
Mechanisms of Resistance
  • None evaluated