Age-related methylation of tumor suppressor and tumor-related genes: an analysis of autopsy samples.
Age-related methylation may have the potential to behave as a mutator process. To clarify the physiological consequence of age-related methylation of tumor suppressor and tumor-related genes, we studied promoter methylation status in non-neoplastic cells of various organs obtained at autopsy by methylation-specific PCR. Promoter methylation status of APC, DAP-kinase, E-cadherin, GSTP1, hMLH1, p16, RASSF1A and RUNX3 genes, which are frequently silenced in certain human malignancies, was studied in non-neoplastic cells of the esophagus, stomach, small and large intestines, liver, pancreas, kidney and lung obtained from 38 Japanese autopsies. The tumor suppressor and tumor-related genes, except APC and RASSF1A, were generally unmethylated in samples obtained from people who were less than 32 years old (n=11). Methylated promoters were present at variable frequencies in a tissue-specific manner in samples obtained from people who were greater than 42 years old (n=27), although GSTP1 and hMLH1 methylation was absent or infrequent and lacked tissue specificity. In the majority of organs, the incidence of age-related methylation paralleled the reported methylation incidence in malignant counterparts. Thus, age-related methylation of a different set of genes is thought to constitute a field defect in different organs.
Waki
Takayoshi
T
Department of Pathology, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata, 990-9585, Japan.
Tamura
Gen
G
Sato
Makoto
M
Motoyama
Teiichi
T
D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001344:Autopsy; D002352:Carrier Proteins; D002478:Cells, Cultured; D002648:Child; D019175:DNA Methylation; D005260:Female; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D007223:Infant; D007527:Isoenzymes / Q000378:metabolism; D007564:Japan; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009363:Neoplasm Proteins / Q000378:metabolism; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D013447:Sulfites / Q000494:pharmacology; D014018:Tissue Distribution
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D007527:Isoenzymes; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D013447:Sulfites; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D000070957:MutL Protein Homolog 1