Switch from Monoallelic to Biallelic Human IGF2 Promoter Methylation during Aging and Carcinogenesis

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 IGF...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1996-10, Vol.93 (21), p.11757-11762
Main Authors: Issa, Jean-Pierre J., Vertino, Paula M., Boehm, Corinne D., Newsham, Irene F., Baylin, Stephen B.
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Aged, 80 and over
Aging - genetics
Alleles
Bone Marrow - metabolism
Breast Neoplasms - genetics
Cell Line
Cell lines
Child
Child, Preschool
Colon - metabolism
Colonic Neoplasms - genetics
Dinucleoside Phosphates
DNA
DNA Methylation
DNA Primers
Enzymes
Female
Genes
Genomics
Humans
Insulin-Like Growth Factor II - biosynthesis
Insulin-Like Growth Factor II - genetics
Leukemia - genetics
Lung Neoplasms - genetics
Lymphocytes - metabolism
Male
Methylation
Middle Aged
Neoplasms - genetics
Polymerase Chain Reaction
Promoter Regions, Genetic
Tumor cell line
Tumor Cells, Cultured
Tumors
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.93.21.11757