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

• Published in: Cellular oncology (Dordrecht) 2014-08, Vol.37 (4), p.245-252
• Main Authors: Yousuf, Adfar, Bhat, Mohammad Younis, Pandith, Arshad A., Afroze, Dil, Khan, Nighat P., Alam, Khursheed, Shah, Parveen, Shah, M. Amin, Mudassar, Syed
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; Cancer Research; DNA Methylation - genetics; DNA Modification Methylases - genetics; DNA Modification Methylases - metabolism; DNA Repair Enzymes - genetics; DNA Repair Enzymes - metabolism; Female; Gene Silencing - physiology; Humans; In Vitro Techniques; India - epidemiology; Male; Middle Aged; Oncology; Original Paper; Pathology; Polymorphism, Single-Stranded Conformational - genetics; Promoter Regions, Genetic - genetics; Risk Factors; Stomach Neoplasms - epidemiology; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism
• ISSN: 2211-3428; 2211-3436
• DOI: 10.1007/s13402-014-0179-3

Purpose 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. Methods 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. Results 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