Scientific Research and Essays

  • Abbreviation: Sci. Res. Essays
  • Language: English
  • ISSN: 1992-2248
  • DOI: 10.5897/SRE
  • Start Year: 2006
  • Published Articles: 2754

Full Length Research Paper

Tissue specific epigenetic silencing of the distinct tumor suppressor genes in lung cancer

  Sulhattin Arslan1, Sule Karadayi2*, Ozturk Ozdemir3, Ekber Sahin4, Semra Ozdemir5 and Ibrahim Akkurt1        
  1Department of Chest Disease, School of Medicine, Cumhuriyet University, Sivas, Turkey. 2Department of Emergency Medicine, School of Medicine, Cumhuriyet University,   Sivas, Turkey. 3Department of Medical Genetics, School of Medicine, Cumhuriyet University,   Sivas, Turkey. 4Cumhuriyet University, School of Medicine, Department of Thoracic Surgery, Sivas, Turkey. 5Department of Nuclear Medicine, Numune Hospital, Sivas, Turkey.
Email: [email protected]

  •  Accepted: 10 March 2010
  •  Published: 31 May 2010

Abstract

 

The role of aberrant methylation of the cytosine-guanine dinucleotide islands in the promoter region of tumor suppressor genes in lung cancer development is increasingly recognized. DNAs extracted from cancer tissue biopsies of 40 patients with lung cancer were used. Methylated sites of tumor suppressor geneswere examined by bisulfate treatment and methylation-specific PCR method. Strip Assay was used to access the promoter profiles of cytosine-guanine dinucleotide islands. Some of the tumor specimens evaluated showed fully inactive methylated pattern profiles for the tumor suppressor genes that were studied and some showed partially inactive methylated patterns. In lung cancers, the prevalence of SFRP2, p16, DAPK1, HIC1, MGMT promoter methylation status were 11/40(27.5), 8/40(20), 30/40(75), 16/40(40%) and 10/40(25%), respectively. DAPK1 gene inactivation was seen in all (5/5, 100%) the adenocarcinoma type of tumors and was fully hypermethylated in 13/19 squamous cell type (68.4%), 6/9 SCLC (66.7%), and 4/7 malign epithelial (57.1%) tumors. Our results confirm the importance of methylation in the molecular pathogenesis of lung cancer with the majority of tumors having one or more tumor suppressor genes islands methylated for some tumor suppressor genes promoters.

 

Key words: Lung carcinoma, tumor suppressor genes, epigenetic alterations.

Abbreviation

 

PCR, Polymerase chain reaction; MSP, methylation specific; TSG, tumor suppressor gene; DAPK1, 
death-associated protein kinase 1; p16, a tumour suppressor gene contributing in cell cycle arrest as cyclin dependent kinase (DAPK2) inhibitor; SFRP2, secreted frizzle-related protein 2; HIC1, hypermethylated in cancer-1; MGMT, O(6)-methylguanine-DNA methyltransferase; 5-mC, epicytosine, 5-methyl cytosine; Ca, cancer.