title: Relationship between promoter methylation & tissue expression of MGMT gene in ovarian cancer.
abstract: OBJECTIVE
  Epigenetic alterations, in addition to multiple gene abnormalities, are involved in the genesis and progression of human cancers. Aberrant methylation of CpG islands within promoter regions is associated with transcriptional inactivation of various tumour suppressor genes. O 6-methyguanine-DNA methyltransferase (MGMT) is a DNA repair gene that removes mutagenic and cytotoxic adducts from the O 6 -position of guanine induced by alkylating agents. MGMT promoter hypermethylation and reduced expression has 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 epithelial ovarian carcinoma.
  
  
  METHODS
  A total of 88 epithelial ovarian cancer (EOC) tissue samples, 14 low malignant potential (LMP) tumours and 20 benign ovarian tissue samples were analysed for MGMT promoter methylation by nested methylation-specific polymerase chain reaction (MSP) after bisulphite modification of DNA. A subset of 64 EOC samples, 10 LMP and benign tumours and five normal ovarian tissue samples were analysed for protein expression by immunohistochemistry.
  
  
  RESULTS
  The methylation frequencies of the MGMT gene promoter were found to be 29.5, 28.6 and 20 per cent for EOC samples, LMP tumours and benign cases, respectively. Positive protein expression was observed in 93.8 per cent of EOC and 100 per cent in LMP, benign tumours and normal ovarian tissue samples. Promoter hypermethylation with loss of protein expression was seen only in one case of EOC.
  
  
  CONCLUSIONS
  Our results suggest that MGMT promoter hypermethylation does not always reflect gene expression.
authors.forename: V
authors.initials: V
authors.lastname: Shilpa
authors.forename: Rahul
authors.initials: R
authors.lastname: Bhagat
authors.forename: C S
authors.initials: CS
authors.lastname: Premalata
authors.forename: V R
authors.initials: VR
authors.lastname: Pallavi
authors.forename: G
authors.initials: G
authors.lastname: Ramesh
authors.affiliation: Department of Biochemistry, Kidwai Memorial Institute of Oncology, Bangalore, India.
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Krishnamoorthy
mesh_terms: D000328:Adult; D000368:Aged; D019175:DNA Methylation / Q000235:genetics*; D015254:DNA Modification Methylases / Q000096:biosynthesis* / Q000235:genetics; D045643:DNA Repair Enzymes / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes