High-resolution DNA copy number and gene expression analyses distinguish chromophobe renal cell carcinomas and renal oncocytomas

BMC Cancer. 2009 May 18:9:152. doi: 10.1186/1471-2407-9-152.

Abstract

Background: The diagnosis of benign renal oncocytomas (RO) and chromophobe renal cell carcinomas (RCC) based on their morphology remains uncertain in several cases.

Methods: We have applied Affymetrix GeneChip Mapping 250 K NspI high-density oligoarrays to identify small genomic alterations, which may occur beyond the specific losses of entire chromosomes, and also Affymetrix GeneChip HG-U133 Plus2.0 oligoarrays for gene expression profiling.

Results: By analysing of DNA extracted from 30 chRCCs and 42 ROs, we have confirmed the high specificity of monosomies of chromosomes 1, 2, 6, 10, 13, 17 and 21 in 70-93% of the chRCCs, while ROs displayed loss of chromosome 1 and 14 in 24% and 5% of the cases, respectively. We demonstrated that chromosomal gene expression biases might correlate with chromosomal abnormalities found in chromophobe RCCs and ROs. The vast majority genes downregulated in chromophobe RCC were mapped to chromosomes 2, 6, 10, 13 and 17. However, most of the genes overexpressed in chromophobe RCCs were located to chromosomes without any copy number changes indicating a transcriptional regulation as a main event.

Conclusion: The SNP-array analysis failed to detect recurrent small deletions, which may mark loci of genes involved in the tumor development. However, we have identified loss of chromosome 2, 10, 13, 17 and 21 as discriminating alteration between chromophobe RCCs and ROs. Therefore, detection of these chromosomal changes can be used for the accurate diagnosis in routine histology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma, Oxyphilic / genetics*
  • Adenoma, Oxyphilic / pathology
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / pathology
  • Chromosomes, Human / genetics
  • Gene Dosage*
  • Gene Expression Profiling*
  • Humans
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / pathology
  • Oligonucleotide Array Sequence Analysis
  • Tumor Cells, Cultured

Associated data

  • GEO/GSE11151