5′ CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancers

Adrian Merlo, James G. Herman, Li Mao, Daniel J. Lee, Edward Gabrielson, Peter C. Burger, Stephen B Baylin, David Sidransky

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)686-692
Number of pages7
JournalNature Medicine
Volume1
Issue number7
StatePublished - 1995

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CpG Islands
Methylation
Tumors
decitabine
Loss of Heterozygosity
Genes
Neoplasms
Chromosomes
Suppressor Genes
Gene Silencing
Tumor Suppressor Genes
Cells
Point Mutation
Tissue
Cell Line

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

5′ CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancers. / Merlo, Adrian; Herman, James G.; Mao, Li; Lee, Daniel J.; Gabrielson, Edward; Burger, Peter C.; Baylin, Stephen B; Sidransky, David.

In: Nature Medicine, Vol. 1, No. 7, 1995, p. 686-692.

Research output: Contribution to journalArticle

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AU - Sidransky, David

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