5' CpG Island Methylation Is Associated With Transcriptional Silencing of the Tumour Suppressor p16/CDKN2/MTS1 in Human Cancers

Nat Med. 1995 Jul;1(7):686-92. doi: 10.1038/nm0795-686.

Abstract

Loss of heterozygosity on chromosome 9p21 is one of the most frequent genetic alterations identified in human cancer. The rate of point mutations of p16, a candidate suppressor gene of this area, is low in most primary tumours with allelic loss of 9p21. Monosomic cell lines with structurally unaltered p16 show methylation of the 5' CpG island of p16. This distinct methylation pattern was associated with a complete transcriptional block that was reversible upon treatment with 5-deoxyazacytidine. Moreover, de novo methylation of the 5' CpG island of p16 was also found in approximately 20% of different primary neoplasms, but not in normal tissues, potentially representing a common pathway of tumour suppressor gene inactivation in human cancers.

Publication types

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

MeSH terms

  • 5-Methylcytosine
  • Alleles
  • Azacitidine / analogs & derivatives
  • Azacitidine / pharmacology
  • Base Sequence
  • Brain Neoplasms / genetics
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Squamous Cell / genetics
  • Carrier Proteins / biosynthesis
  • Carrier Proteins / genetics*
  • Carrier Proteins / physiology
  • Chromosomes, Human, Pair 9
  • CpG Islands*
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cytosine / analogs & derivatives*
  • Cytosine / physiology
  • DNA, Neoplasm / genetics*
  • Decitabine
  • Gene Expression Regulation, Neoplastic* / drug effects
  • Genes, Tumor Suppressor*
  • Glioma / genetics
  • Head and Neck Neoplasms / genetics
  • Humans
  • Lung Neoplasms / genetics
  • Methylation
  • Molecular Sequence Data
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / physiology
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Sequence Deletion
  • Transcription, Genetic / drug effects
  • Tumor Cells, Cultured

Substances

  • Carrier Proteins
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Neoplasm
  • Neoplasm Proteins
  • 5-Methylcytosine
  • Decitabine
  • Cytosine
  • Azacitidine