TY - JOUR
T1 - Switch from monoallelic to biallelic human IGF2 promoter methylation during aging and carcinogenesis
AU - Issa, Jean Pierre J.
AU - Vertino, Paula M.
AU - Boehm, Corinne D.
AU - Newsham, Irene F.
AU - Baylin, Stephen B.
PY - 1996/10/15
Y1 - 1996/10/15
N2 - 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.
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.
KW - DNA methylation
KW - cancer
KW - imprinting
UR - http://www.scopus.com/inward/record.url?scp=0029976873&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029976873&partnerID=8YFLogxK
U2 - 10.1073/pnas.93.21.11757
DO - 10.1073/pnas.93.21.11757
M3 - Article
C2 - 8876210
AN - SCOPUS:0029976873
SN - 0027-8424
VL - 93
SP - 11757
EP - 11762
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 21
ER -