Bap1 and Pbrm1: Determinants of Tumor Grade and mTOR Activation in VHL-Deficient Mouse Models of Renal Cell Carcinoma

Cancer Discov. 2017 Aug;7(8):802-804. doi: 10.1158/2159-8290.CD-17-0610.

Abstract

<b/> Large genome sequencing efforts have identified frequent mutations in the histone-modifying and chromatin-remodeling genes BAP1 and PBRM1 in clear cell renal cell carcinoma (ccRCC). In this issue of Cancer Discovery, Gu and colleagues model these genetic events in mice and report that dual inactivation of Vhl with either Bap1 or Pbrm1 results in faithful genetically engineered murine models of ccRCC. Moreover, their work establishes that Bap1 and Pbrm1 are determinants of tumor grade and mTORC1 activation and provocatively suggests that the cell of origin of ccRCC may lie in PAX8-expressing Bowman capsule cells. Cancer Discov; 7(8); 802-4. ©2017 AACRSee related article by Gu et al., p. 900.

Publication types

  • Comment

MeSH terms

  • Animals
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / pathology
  • Chromatin Assembly and Disassembly / genetics
  • DNA-Binding Proteins
  • Disease Models, Animal
  • Genetic Engineering
  • HMGB Proteins / genetics*
  • Histone Code / genetics
  • Humans
  • Mechanistic Target of Rapamycin Complex 1 / genetics
  • Mice
  • Mice, Transgenic / genetics
  • Mutation
  • Transcription Factors
  • Tumor Suppressor Proteins / genetics*
  • Ubiquitin Thiolesterase / genetics*
  • Von Hippel-Lindau Tumor Suppressor Protein / genetics*

Substances

  • BAP1 protein, mouse
  • DNA-Binding Proteins
  • HMGB Proteins
  • Pbrm1 protein, mouse
  • Transcription Factors
  • Tumor Suppressor Proteins
  • Von Hippel-Lindau Tumor Suppressor Protein
  • Mechanistic Target of Rapamycin Complex 1
  • Ubiquitin Thiolesterase
  • VHL protein, mouse