BAP1, PBRM1 and SETD2 in clear-cell renal cell carcinoma: molecular diagnostics and possible targets for personalized therapies

Expert Rev Mol Diagn. 2015;15(9):1201-10. doi: 10.1586/14737159.2015.1068122. Epub 2015 Jul 11.


Several novel recurrent mutations of histone modifying and chromatin remodeling genes have been identified in renal cell carcinoma. These mutations cause loss of function of several genes located in close proximity to VHL and include PBRM1, BAP1 and SETD2. PBRM1 encodes for BAF180, a component of the SWI/SNF chromatin remodeling complex, and is inactivated in, on average, 36% of clear cell renal cell carcinoma (ccRCC). Mutations of BAP1 encode for the histone deubiquitinase BRCA1 associated protein-1, and are present in 10% of ccRCCs. They are largely mutually exclusive with PBRM1 mutations. Mutations to SETD2, a histone methyltransferase, occur in 10% of ccRCC. BAP1- or SETD2-mutated ccRCCs have been associated with poor overall survival, while PBRM1 mutations seem to identify a favorable group of ccRCC tumors. This review describes the roles of PBRM1, BAP1 and SETD2 in the development and progression of ccRCC and their potential for future personalized approaches.

Keywords: BRCA1-associated protein-1; Polybromo-1; SETD2; clear cell renal cell carcinoma; molecular diagnostics; personalized therapies.

Publication types

  • Review

MeSH terms

  • Animals
  • Carcinoma, Renal Cell / diagnosis*
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / therapy
  • DNA-Binding Proteins
  • Drug Resistance, Neoplasm / genetics
  • Epigenesis, Genetic
  • Epigenomics / methods
  • Genetic Predisposition to Disease
  • Germ-Line Mutation
  • Histone-Lysine N-Methyltransferase / genetics*
  • Humans
  • Kidney Neoplasms / diagnosis*
  • Kidney Neoplasms / genetics*
  • Molecular Diagnostic Techniques
  • Molecular Targeted Therapy
  • Mutation
  • Mutation Rate
  • Nuclear Proteins / genetics*
  • Precision Medicine
  • Prognosis
  • Radiation Tolerance / genetics
  • Transcription Factors / genetics*
  • Tumor Suppressor Proteins / genetics*
  • Ubiquitin Thiolesterase / genetics*


  • BAP1 protein, human
  • DNA-Binding Proteins
  • Nuclear Proteins
  • PBRM1 protein, human
  • Transcription Factors
  • Tumor Suppressor Proteins
  • Histone-Lysine N-Methyltransferase
  • SETD2 protein, human
  • Ubiquitin Thiolesterase