Gender Specific Mutation Incidence and Survival Associations in Clear Cell Renal Cell Carcinoma (CCRCC)

PLoS One. 2015 Oct 20;10(10):e0140257. doi: 10.1371/journal.pone.0140257. eCollection 2015.


Renal cell carcinoma (RCC) is diagnosed in >200,000 individuals worldwide each year, accounting for ~2% of all cancers, but the spread of this disease amongst genders is distinctly uneven. In the U.S. the male:female incidence ratio is approximately 2:1. A potential hypothesis is mutation spectra may differ between tumors dependent upon the gender of the patient, such as mutations of X chromosome encoded genes being more prevalent in male-derived tumors. Combined analysis of three recent large-scale clear cell renal cell carcinoma (CCRCC) mutation sequencing projects identified a significantly increased mutation frequency of PBRM1 and the X chromosome encoded KDM5C in tumors from male patients and BAP1 in tumors from female patients. Mutation of BAP1 had previously been significantly associated with poorer overall survival; however, when stratified by gender, mutation of BAP1 only significantly affected overall survival in female patients. Mutation of chromatin remodeling genes alters gene regulation, but the overall effect of these alterations may also be modified by the presence of other gender specific factors. Thus, the combination of gender and mutation of a specific gene, such as BAP1, may have implications not only for prognosis but also for understanding the role of chromatin remodeling gene mutations in kidney cancer progression.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Carcinoma, Renal Cell / genetics*
  • Chromatin Assembly and Disassembly / genetics
  • Cohort Studies
  • Disease Progression
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease / genetics*
  • Histone Demethylases / genetics
  • Humans
  • Kaplan-Meier Estimate
  • Kidney Neoplasms / genetics*
  • Male
  • Mutation*
  • Nuclear Proteins / genetics
  • Prognosis
  • Sex Factors
  • Survival Analysis
  • Transcription Factors / genetics
  • Tumor Suppressor Proteins / genetics
  • Ubiquitin Thiolesterase / genetics


  • BAP1 protein, human
  • Nuclear Proteins
  • PBRM1 protein, human
  • Transcription Factors
  • Tumor Suppressor Proteins
  • Histone Demethylases
  • KDM5C protein, human
  • Ubiquitin Thiolesterase