title: Promoter Hypermethylation and Its Impact on Expression of MGMT Gene in the GIT Malignant Patients of Kashmiri Origin.
abstract: Epigenetic alterations, in addition to multiple gene abnormalities, are involved in the genesis and progression of human cancers. Gastrointestinal tract (GIT) cancer is a major medical and economic burden worldwide. Aberrant methylation of CpG islands within promoter regions is associated with transcriptional inactivation of various tumor suppressor genes. Although a number of cancer-associated genes have been found to be hypermethylated in GIT cancer, valuable methylation markers for early diagnosis and prognostic evaluation of this cancer remain largely unknown. O6-methyguanine DNA methyltransferase (MGMT) is a DNA-repair gene that removes mutagenic and cytotoxic adducts from the O6 position of guanine induced by alkylating agents. MGMT promoter hypermethylation and reduced expression have been found in some primary human carcinomas. We studied DNA methylation of CpG islands of the MGMT gene and its relation with MGMT protein expression in human GIT carcinomas. A total of 210 GIT tumor samples and 90 adjacent normal tissues were analyzed for MGMT promoter methylation by methylation-specific polymerase chain reaction after bisulfite modification of DNA and same samples were analyzed for MGMT protein expression by Western blotting. The methylation frequencies of MGMT gene promoter were 41.4%, 34.2%, and 44.2% in stomach, esophageal, and colorectal cancer cases while as 16.6, 13.3, and 13.3 in respective controls. MGMT protein was found downregulated in controls of all GIT. The results suggest that methylation at CpG islands of MGMT may be responsible for the downregulation of MGMT protein expression in GIT cancers.
authors.affiliation: a Department of Biochemistry , Government Medical College Srinagar , Srinagar , India.
authors.forename: Arif Akbar
authors.initials: AA
authors.lastname: Bhat
authors.affiliation: b Multidisciplinary Research Unit , Government Medical College Srinagar , Srinagar , India.
authors.forename: Hilal Ahmad
authors.initials: HA
authors.lastname: Wani
authors.affiliation: a Department of Biochemistry , Government Medical College Srinagar , Srinagar , India.
authors.forename: Shiekh
authors.initials: S
authors.lastname: Ishaq
authors.affiliation: c Department of Biotechnology , University of Kashmir , Hazratbal Srinagar , India.
authors.forename: Ajaz Ahmad
authors.initials: AA
authors.lastname: Waza
authors.affiliation: d Department of Human Genetics , Punjabi University , Patiala , India.
authors.forename: Rawoof Ahmad
authors.initials: RA
authors.lastname: Malik
authors.affiliation: a Department of Biochemistry , Government Medical College Srinagar , Srinagar , India.
authors.forename: Iram
authors.initials: I
authors.lastname: Shabir
authors.affiliation: e Department of Surgery , Government Medical College Srinagar , Srinagar , India.
authors.forename: Showkat
authors.initials: S
authors.lastname: Jeelani
authors.affiliation: f Department of Medicine , Government Medical College Srinagar , Srinagar , India.
authors.forename: Showkat
authors.initials: S
authors.lastname: Kadla
authors.affiliation: g Registrar , Government Medical College Srinagar , Srinagar , India.
authors.forename: Waseem
authors.initials: W
authors.lastname: Qureshie
authors.affiliation: h Department of Biochemistry , University of Kashmir , Srinagar , India.
authors.forename: Akbar
authors.initials: A
authors.lastname: Masood
authors.affiliation: a Department of Biochemistry , Government Medical College Srinagar , Srinagar , India.
authors.forename: Sabhiya
authors.initials: S
authors.lastname: Majid
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D018899:CpG Islands; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000096:biosynthesis / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000096:biosynthesis / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D005006:Ethnicity / Q000235:genetics; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics*; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes
keywords: CpG Island; DNA methylation; Epigenetics; Gastrointestinal tract cancer; Methylation-specific PCR