Array CGH demonstrates characteristic aberration signatures in human papillary thyroid carcinomas governed by RET/PTC

Oncogene. 2008 Jul 31;27(33):4592-602. doi: 10.1038/onc.2008.99. Epub 2008 Apr 14.

Abstract

The aim of this study is to investigate additional genetic alterations in papillary thyroid carcinomas (PTCs) with known RET/PTC rearrangements. We applied array-based comparative genomic hybridization (array CGH) to 33 PTC (20 PTC from adults, 13 post-Chernobyl PTC from children) with known RET/PTC status. Principal component analysis and hierarchical cluster analysis identified cases with similar aberration patterns. Significant deviations between tumour-groups were obtained by statistical testing (Fisher's exact test in combination with Benjamini-Hochberg FDR-controlling procedure). FISH analysis on FFPE sections was applied to validate the array CGH data. Deletions were found more frequently in RET/PTC-positive and RET/PTC-negative tumours than amplifications. Specific aberration signatures were identified that discriminated between RET/PTC-positive and RET/PTC-negative cases (aberrations on chromosomes 1p, 3q, 4p, 7p, 9p/q, 10q, 12q, 13q and 21q). In addition, childhood and adult RET/PTC-positive cases differ significantly for a deletion on the distal part of chromosome 1p. There are additional alterations in RET/PTC-positive tumours, which may act as modifiers of RET activation. In contrast, alterations in RET/PTC-negative tumours indicate alternative routes of tumour development. The data presented serve as a starting point for further studies on gene expression and function of genes identified in this study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Carcinoma, Papillary / genetics*
  • Chernobyl Nuclear Accident*
  • Child
  • Chromosome Aberrations*
  • Chromosomes, Human / genetics*
  • DNA-Binding Proteins / genetics*
  • Female
  • Humans
  • In Situ Hybridization, Fluorescence / methods
  • Male
  • Neoplasms, Radiation-Induced / genetics*
  • Nuclear Proteins / genetics*
  • Thyroid Neoplasms / genetics*

Substances

  • DNA-Binding Proteins
  • Nuclear Proteins
  • TRIM27 protein, human