NDLI: MGMT gene silencing by promoter hypermethylation in gastric cancer in a high incidence area

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MGMT gene silencing by promoter hypermethylation in gastric cancer in a high incidence area

Content Provider	Springer Nature Link
Author	Yousuf, Adfar Bhat, Mohammad Younis Pandith, Arshad A. Afroze, Dil Khan, Nighat P. Alam, Khursheed Shah, Parveen Shah, M. Amin Mudassar, Syed
Copyright Year	2014
Abstract	Inactivation of tumor suppressor and DNA repair genes by promoter hypermethylation does commonly occur in human cancers. O$^{6}$-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme that removes methyl groups as well as larger adducts at the O$^{6}$ position of guanine. In the absence of MGMT activity, O$^{6}$-methylguanine mispairs with thymine during DNA replication, resulting in G:C to A:T transitions. Promoter hypermethylation of the MGMT gene has been observed in various cancers, including gastric cancer. Here, we aimed at assessing the promoter hypermethylation, mutation and expression status of the MGMT gene in patients from a geographic region with a high incidence of gastric cancer (Kashmir, North India) and to investigate their association with various clinicopathological characteristics.In this study 82 gastric cancer samples and adjacent normal tissues were included. Mutations in the MGMT gene were detected by single stranded conformational polymorphism (SSCP) analysis and direct sequencing. Methylation-specific polymerase chain reaction (MS-PCR) and Western blot analyses were performed to detect promoter hypermethylation and concomitant (loss of) expression of the MGMT gene.Promoter hypermethylation of the MGMT gene was found in 52.44 % (43 of 82) of the tumor samples and loss of MGMT protein expression was detected in 45.12 % (37 of 82) of the tumor samples. Hypermethylation and loss of expression were significantly associated with higher tumor grades (moderately/poorly differentiated) (P < 0.05) and higher tumor stages (III/IV) (P < 0.05). In addition, MGMT hypermethylation and loss of expression were found to be significantly associated with high salt tea consumption (P < 0.05).Our results indicate that MGMT promoter hypermethylation and concomitant loss of MGMT protein expression may play an important role in the development of gastric cancer in the Kashmiri population. High salt tea consumption may be a risk factor.
Starting Page	245
Ending Page	252
Page Count	8
File Format	PDF
ISSN	22113428
Journal	Cellular Oncology
Volume Number	37
Issue Number	4
e-ISSN	22113436
Language	English
Publisher	Springer Netherlands
Publisher Date	2014-07-10
Publisher Institution	International Society for Cellular Oncology
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Gastric cancer MGMT Hypermethylation Kashmiri population MS-PCR Cancer Research Biomedicine general Pathology Oncology
Content Type	Text
Resource Type	Article
Subject	Cancer Research Molecular Medicine Oncology

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