Jpj. Issa et al., SWITCH FROM MONOALLELIC TO BIALLELIC HUMAN IGF2 PROMOTER METHYLATION DURING AGING AND CARCINOGENESIS, Proceedings of the National Academy of Sciences of the United Statesof America, 93(21), 1996, pp. 11757-11762
We have previously linked aging, carcinogenesis, and de novo methylati
on within the promoter of the estrogen receptor (ER) gene in human col
on. We now examine the dynamics of this process for the imprinted gene
for insulin-like growth factor II (IGF2). In young individuals, the P
2-4 promoters of IGF2 are methylated exclusively on the silenced mater
nal allele. During aging, this promoter methylation becomes more exten
sive and involves the originally unmethylated allele. Most adult human
tumors, including colon, breast, lung, and leukemias, exhibit increas
ed methylation at the P2-4 IGF2 promoters, suggesting further spreadin
g during the neoplastic process. In tumors, this methylation is associ
ated 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 promote
r of the IGF2 gene during aging and carcinogenesis, and provide furthe
r evidence for a potential link between aberrant methylation and disea
ses of aging.