Meta-analysis of adrenocortical tumour genomics data: Novel pathogenic pathways revealed

P. M. Szabó, V. Tamási, V. Molnár, M. Andrásfalvy, Z. Tömböl, R. Farkas, K. Kövesdi, A. Patócs, M. Tóth, C. Szalai, A. Falus, K. Rácz, P. Igaz

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Sporadic adrenocortical tumours are common, but their pathogenesis is poorly elucidated. In this study, we present a meta-analysis and review of gene expression microarray and comparative genome hybridization (CGH) studies performed to date on these tumours, including our own data. Data of whole genome microarray studies from altogether 164 tumours (97 benign, 67 malignant) and 18 normal tissues were reclassified and reanalysed. Significant gene sets and cytogenetic changes from publications without available genomic data were also examined including 269 benign, 215 malignant tumour and 30 normal tissues. In our experimental study, 11 tumour and four normal samples were analysed by parallel mRNA and CGH profiling. Data were examined by an integrative bioinformatics approach (GeneSpring, Gene Set Enrichment Analysis and Ingenuity Pathway Analysis softwares) searching for common gene expression changes and paralleling chromosome aberrations. Both meta-analysis of available mRNA and CGH profiling data and our experimental study revealed three major pathogenetic pathways: (1) cell cycle, (2) retinoic acid signalling (including lipopolysaccharide/Toll like receptor 4 pathway), (3) complement system and antigen presentation. These pathways include novel, previously undescribed pathomechanisms of adrenocortical tumours, and associated gene products may serve as diagnostic markers of malignancy and therapeutic targets.

Original languageEnglish
Pages (from-to)3163-3172
Number of pages10
JournalOncogene
Volume29
Issue number21
DOIs
Publication statusPublished - May 27 2010

Keywords

  • Adrenocortical tumour
  • Comparative genome hybridization
  • MRNA profiling
  • Meta-analysis
  • Pathway analysis

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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