Aberrant methylation as a main mechanism of TSGs silencing in PTC

Front Biosci (Elite Ed). 2011 Jan 1;3:137-57. doi: 10.2741/e228.

Abstract

In the present study the role of tumour suppressor genes (TSGs) hypermethylation and genetic instability of LOH/MSI type in thyroid tumorigenesis was assessed. Expression, methylation status and presence of LOH/MSI were analyzed for 8 TSGs selected from imprinted (IR) and non-imprinted (NIR) chromosomal regions in papillary thyroid carcinomas (PTCs) and nodular goitres (NGs). The results show that methylation-induced gene silencing occurs at an early step of thyroid carcinogenesis and involves multiple genes. Genetic changes of LOH/MSI type are less frequent. In PTC samples, the lack of significant differences in the frequency of LOH in IR and NIR suggests that it is not a key mechanism changing the pattern of gene expression. Co-methylation observed both in NG and PTC raises a possibility that, in thyroid tissue, methylation-induced silencing may occur not only in malignant transformation but also in functional context. We did not recognize any of the studied TSGs - in regard to aberrant methylation status or LOH/MSI frequency - as a selective molecular marker in thyroid tumorigenesis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Base Sequence
  • Carcinoma
  • Carcinoma, Papillary
  • DNA Methylation / physiology*
  • DNA Primers / genetics
  • Female
  • Gene Silencing / physiology*
  • Genes, Tumor Suppressor / physiology*
  • Humans
  • Male
  • Microsatellite Repeats / genetics
  • Middle Aged
  • Molecular Sequence Data
  • Poland
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • Spectrophotometry
  • Statistics, Nonparametric
  • Sulfites
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / physiopathology

Substances

  • DNA Primers
  • Sulfites
  • sodium bisulfite