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Cancer. 2001 Jun 15;91(12):2294-301.

Concurrent hypermethylation of multiple tumor-related genes in gastric carcinoma and adjacent normal tissues.

Author information

1
Department of Medicine & Therapeutics, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR. wkleung@cuhk.edu.hk

Abstract

BACKGROUND:

Transcriptional silencing by CpG-island hypermethylation now is believed to be an important mechanism of tumorigenesis. To date, studies on CpG-island hypermethylation in gastric carcinoma and adjacent normal tissues are few.

METHODS:

The authors examined 5 gastric carcinoma cell lines, 26 frozen gastric carcinoma tissues and their adjacent nontumor area for concurrent CpG-island hypermethylation in 6 tumor-related genes (p15, p16, E-cadherin, GST-pi, hMLH1, and VHL) by methylation-specific polymerase chain reaction. Nontumorous gastric tissues from 10 gastritis patients were used as controls.

RESULTS:

Hypermethylation was not detected in any tissue taken from gastritis patients but was identified in all 5 cell lines and in 24 (92.3%) gastric carcinoma patients. CpG-island methylation in tumor-related genes also was detected in 7 out of the 25 adjacent normal tissues from cancer patients. Hypermethylation of E-cadherin, p15, and p16 were detected more frequently than GST-pi and hMLH1, whereas aberrant methylation of VHL was not detected. Concurrent hypermethylation in 2 or more tumor-related genes was detected in 3 out of the 5 gastric carcinoma cell lines, 22 (84.6%) tumor samples, and 5 (20%) adjacent gastric tissues. Eighteen (69.2%) tumor samples showed hypermethylation in >or= 3 genes.

CONCLUSIONS:

The current study showed that concurrent hypermethylation of multiple tumor-related genes is detected frequently in gastric carcinoma and adjacent normal tissues. Study findings suggested that a mechanism that leads to dysregulation in CpG-island methylation is likely to be involved in the early gastric carcinogenesis process.

PMID:
11413518
[Indexed for MEDLINE]

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