Publication: Promoter methylation status of tumor suppressor and tumor-related genes in
neoplastic and non-neoplastic gastric epithelia
Authors
Tamura, G.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
A number of tumor suppressor and tumorrelated
genes exhibit promoter hypermethylation with
resulting gene silencing in human cancers. In addition,
several gene promoters have also been shown to become
hypermethylated in non-neoplastic cells during aging. To
assess the physiological consequence and clinical
significance of gene promoter methylation in gastric
epithelia, our laboratory has studied the methylation
status of tumor suppressor and tumor-related genes,
including APC, DAP-kinase, DCC, E-cadherin, GSTP1,
hMLH1, p16, PTEN, RASSF1A, RUNX3 and TSLC1, in
neoplastic and non-neoplastic gastric epithelia. The
tumor suppressor and tumor-related genes, except APC,
were generally unmethylated in non-neoplastic gastric
epithelia obtained from younger individuals. The
frequencies of methylation increased with age to varying
degrees in various genes, although GSTP1 and PTEN
methylation was completely absent in both neoplastic
and non-neoplastic gastric epithelia. The methylation
frequencies in each gene were found to be comparable in
neoplastic and non-neoplastic gastric epithelia, except
the methylation of RUNX3 and TSLC1, which was
mostly cancer-specific (P<0.01). When methylation
frequencies were compared between non-neoplastic
gastric epithelia from cancer-bearing and non-cancerbearing
stomachs, hMLH1 and p16 methylation was
more frequent in those from cancer-bearing stomachs
(P<0.01). Promoter methylation in tumor suppressor and
tumor-related genes initially occurs in non-neoplastic gastric epithelia, increases with age, and ultimately
silences gene function to constitute a field-defect that
may predispose tissues to gastric cancer evolution. In
clinical applications RUNX3 and TSLC1 methylation
may be utilized as molecular diagnostic markers, and
hMLH1 and p16 methylation as predictors of
malignancy in the stomach.
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