Specific genomic aberrations predict survival, but low mutation rate in cancer hot spots, in clear cell renal cell carcinoma

Appl Immunohistochem Mol Morphol. May-Jun 2015;23(5):334-42. doi: 10.1097/PAI.0000000000000087.


Detailed genetic profiling of clear cell renal cell carcinoma (ccRCC) has revealed genomic regions commonly affected by structural changes and a general genetic heterogeneity. VHL and PBRM1, both located at chromosome 3p, are 2 major genes mutated at high frequency but apart from these aberrations, the mutational landscape in ccRCC is largely undefined. Potential prognostic information given by the genomic changes appears to depend on the particular cohort studied. We analyzed a Swedish ccRCC cohort of 74 patients and found common changes (loss or gain occurring in >20% of the tumors) in 12 chromosomal regions (1p, 3p, 3q, 5q, 6q, 7p, 7q 8p, 9p, 9q, 10q, and 14q). A poor outcome was associated with gain of 7q and losses on 9p, 9q, and 14q. These aberrations were more frequent in metastasized tumors, suggesting alterations of genes important for tumor progression. Sequencing of 48 genes implicated in cancer revealed that only VHL, TP53, and PTEN were mutated at a noticeable frequency (51%, 9%, and 9%, respectively). Shorter relative telomere length (RTL) has been associated with loss of specific chromosomal regions in ccRCC tumors, but we could not verify this finding. However, a significantly lower tumor/nontumor (T/N) RTL ratio was detected for tumors with losses in 4q or 9p. In conclusion, poor outcome in ccRCC was associated with gain of 7q and loss on 9p, 9q, and 14q, whereas the mutation rate overall was low in a screen of cancer-associated genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Renal Cell / diagnosis*
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / mortality
  • Carcinoma, Renal Cell / pathology
  • Chromosome Aberrations*
  • Chromosomes, Human, Pair 14
  • Chromosomes, Human, Pair 3
  • Chromosomes, Human, Pair 7
  • Chromosomes, Human, Pair 9
  • DNA-Binding Proteins
  • Female
  • Gene Expression
  • Genetic Heterogeneity
  • Humans
  • Kidney Neoplasms / diagnosis*
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Mutation Rate*
  • Nuclear Proteins / genetics
  • PTEN Phosphohydrolase / genetics
  • Prognosis
  • Survival Analysis
  • Telomere Homeostasis
  • Transcription Factors / genetics
  • Tumor Suppressor Protein p53 / genetics
  • Von Hippel-Lindau Tumor Suppressor Protein / genetics


  • DNA-Binding Proteins
  • Nuclear Proteins
  • PBRM1 protein, human
  • TP53 protein, human
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • Von Hippel-Lindau Tumor Suppressor Protein
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • VHL protein, human