Genetic characterization of Polish ccRCC patients: somatic mutation analysis of PBRM1, BAP1 and KDMC5, genomic SNP array analysis in tumor biopsy and preliminary results of chromosome aberrations analysis in plasma cell free DNA

Oncotarget. 2017 Apr 25;8(17):28558-28574. doi: 10.18632/oncotarget.15331.


Background: Mutation analysis and cytogenetic testing in clear cell renal cell carcinoma (ccRCC) is not yet implemented in a routine diagnostics of ccRCC.

Material and methods: We characterized the chromosomal alterations in 83 ccRCC tumors from Polish patients using whole genome SNP genotyping assay. Moreover, the utility of next generation sequencing of cell free DNA (cfDNA) in patients plasma as a potential tool for non-invasive cytogenetic analysis was tested. Additionally, tumor specific somatic mutations in PBRM1, BAP1 and KDM5C were determined.

Results: We confirmed a correlation between deletions at 9p and higher tumor size, and deletion of chromosome 20 and the survival time. In Fuhrman grade 1, only aberrations of 3p and 8p deletion, gain of 5q and 13q and gains of chromosome 7 and 16 were present. The number of aberrations increased with Fuhrman grade, all chromosomes displayed cytogenetic changes in G3 and G4. ccRCC specific chromosome aberrations were observed in cfDNA, although discrepancies were found between cfDNA and tumor samples. In total 12 common and 94 rare variants were detected in PBRM1, BAP1 and KDM5C, with four potentially pathogenic variants. We observed markedly lower mutation load in PBRM1.

Conclusions: Cytogenetic analysis of cfDNA may allow more accurate diagnosis of tumor aberrations and therefore the correlation between the chromosome aberrations in cfDNA and clinical outcome should be studied in larger cohorts. The functional studies on in BAP1, KDM5C, PBRM1 mutations in large, independent sample set would be necessary for the assessment of their prognostic and diagnostic potential.

Keywords: SNP microarrays; SNV; ccRCC; cell free DNA; chromatin remodeling.

MeSH terms

  • Carcinoma, Renal Cell / epidemiology*
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / mortality
  • Carcinoma, Renal Cell / pathology
  • Chromosome Aberrations
  • Circulating Tumor DNA
  • DNA Copy Number Variations
  • DNA Mutational Analysis
  • DNA-Binding Proteins
  • Female
  • Genetic Association Studies*
  • Genetic Predisposition to Disease*
  • Genetic Variation*
  • Histone Demethylases / genetics
  • Humans
  • Liquid Biopsy
  • Male
  • Mutation
  • Neoplasm Grading
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Nuclear Proteins / genetics
  • Poland / epidemiology
  • Polymorphism, Single Nucleotide
  • Prognosis
  • Transcription Factors / genetics
  • Tumor Suppressor Proteins / genetics
  • Ubiquitin Thiolesterase / genetics


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