ΔmtDNA4977 Is More Common in Non-tumoral Cells from Gastric Cancer Sample
Received 20 October 2005; accepted 3 February 2006.
Background
The aim of this study was to determine the frequency of ΔmtDNA4977 in tumoral cells as compared with adjacent normal cells in gastric cancer.
Methods
In order to investigate whether a high incidence of mutation exists in mitochondrial DNA of gastric cancer tissues, we screened one of common region of the mitochondrial genome by PCR amplification and Southern blot followed by DNA sequence analysis. DNA isolated from these cells was used to amplify hypervariable regions ATPase8/6, COXIII, ND3, ND4 and ND5 of ΔmtDNA4977.
Results
In 107 cancer patients, ΔmtDNA4977 was detected in 6 cases (5.60%) of the tumoral tissues and 18 cases (16.82%) of the non-tumoral tissues that were adjacent to the tumors. Levels of ΔmtDNA4977 deletions were found to be more in non-tumoral tissues than in adjacent tumoral tissues. There was no correlation of patients with certain clinical parameters like age, sex, tumor location and tumor size; however, there was an obvious relationship with intestinal-type of gastric cancer.
Conclusions
Unknown genetic aspects, ambiguous environmental factors and reactive oxygen species (ROS) can cause the ΔmtDNA4977 mutation rate to be increased in gastric cancer. The results suggest that percentage level of ΔmtDNA4977 is less common and intolerable in tumoral tissue, probably because of high metabolism and ROS generation. We supposed that the cells initially had ΔmtDNA4977 transform to tumoral cells and the existed deletion conferred metabolic disadvantage; thus, cells containing such a mtDNA deletion would be overgrown by other cancer cells without this mtDNA deletion. As a result, the presence of ΔmtDNA4977 will be low in tumoral cells.
aDepartment of Medical Genetics, National Institute for Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran
bDepartment of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Putra, Malaysia
cDepartment of Pathology, Baghyatolah Hospital, Tehran, Iran
Address reprint requests to: Massoud Houshmand, Head, Molecular Genetic Diagnostic Department, Department of Medical Genetics, National Institute for Genetic Engineering and Biotechnology, Pajoohesh Blvd. Tehran-Karaj Highway, 17th Km, P.O. Box:14155-6343, Tehran, Iran
ABSTRACT