Switch from monoallelic to biallelic human IGF2 promoter methylation during aging and carcinogenesis

Jean Pierre J. Issa, Paula M. Vertino, Corinne D. Boehm, Irene F. Newsham, Stephen B. Baylin

Research output: Contribution to journalArticle

209 Citations (Scopus)

Abstract

We have previously linked aging, carcinogenesis, and de novo methylation within the promoter of the estrogen receptor (ER) gene in human colon. We now examine the dynamics of this process for the imprinted gene for insulin-like growth factor II (IGF2). In young individuals, the P2-4 promoters of IGF2 are methylated exclusively on the silenced maternal allele. During aging, this promoter methylation becomes more extensive and involves the originally unmethylated allele. Most adult human tumors, including colon, breast, lung, and leukemias, exhibit increased methylation at the P2-4 IGF2 promoters, suggesting further spreading during the neoplastic process. In tumors, this methylation is associated with diminished or absent IGF2 expression from the methylated P3 promoter but maintained expression from P1, an upstream promoter that is not contained within the IGF2 CpG island. Our results demonstrate a remarkable evolution of methylation patterns in the imprinted promoter of the IGF2 gene during aging and carcinogenesis, and provide further evidence for a potential link between aberrant methylation and diseases of aging.

Original languageEnglish (US)
Pages (from-to)11757-11762
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number21
DOIs
StatePublished - Oct 15 1996

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Methylation
Carcinogenesis
Colon
Alleles
Genes
Neoplastic Processes
CpG Islands
Insulin-Like Growth Factor II
Estrogen Receptors
Neoplasms
Leukemia
Breast
Mothers
Lung

Keywords

  • DNA methylation
  • cancer
  • imprinting

ASJC Scopus subject areas

  • General

Cite this

Switch from monoallelic to biallelic human IGF2 promoter methylation during aging and carcinogenesis. / Issa, Jean Pierre J.; Vertino, Paula M.; Boehm, Corinne D.; Newsham, Irene F.; Baylin, Stephen B.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 93, No. 21, 15.10.1996, p. 11757-11762.

Research output: Contribution to journalArticle

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AB - We have previously linked aging, carcinogenesis, and de novo methylation within the promoter of the estrogen receptor (ER) gene in human colon. We now examine the dynamics of this process for the imprinted gene for insulin-like growth factor II (IGF2). In young individuals, the P2-4 promoters of IGF2 are methylated exclusively on the silenced maternal allele. During aging, this promoter methylation becomes more extensive and involves the originally unmethylated allele. Most adult human tumors, including colon, breast, lung, and leukemias, exhibit increased methylation at the P2-4 IGF2 promoters, suggesting further spreading during the neoplastic process. In tumors, this methylation is associated with diminished or absent IGF2 expression from the methylated P3 promoter but maintained expression from P1, an upstream promoter that is not contained within the IGF2 CpG island. Our results demonstrate a remarkable evolution of methylation patterns in the imprinted promoter of the IGF2 gene during aging and carcinogenesis, and provide further evidence for a potential link between aberrant methylation and diseases of aging.

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