ΔmtDNA⁴⁹⁷⁷ Is More Common in Non-tumoral Cells from Gastric Cancer Sample

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.

Key Words: ΔmtDNA⁴⁹⁷⁷, Gastric cancer, Tumoral cell