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

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.

authors

Issa JP,Vertino PM,Boehm CD,Newsham IF,Baylin SB

doi

10.1073/pnas.93.21.11757

subject

Has Abstract

pub_date

1996-10-15 00:00:00

pages

11757-62

issue

21

eissn

0027-8424

issn

1091-6490

journal_volume

93

pub_type

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