摘要
In order to disclose the relationship between mutations of mitochondrial DNA (mtDNA) and gastric car-cinogenesis, we screened the entire mtDNA sequence in 30 cases of human gastric cancer and matched normal tissues by using denaturing high-performance liquid chromatogra-phy (DHPLC) and DNA sequencing. Our data showed that high frequency (66.7%, 20/30) of mitochondrial genome mutation occurred in gastric cancer. Among these variants, 17 cases (56.7%, 17/30) were identified to be somatic mutation. High level mutant frequency was found in ND4, ND5 coding genes and D-loop control region, which was 36.7%, 26.7% and 30% respectively. Comparing with complexes Ⅲ, Ⅳ and V of the electron transport chain, we found that variants appeared to be more frequent in the subunit genes of complex I. Most of mutations were base substitutions (85.4%, 41/48). Our results suggested that mutations of subunit genes encoding complex I, especially MM, ND4 and ND5 genes, might contribute to human gastric carcinogenesis.
In order to disclose the relationship between mutations of mitochondrial DNA (mtDNA) and gastric carcinogenesis, we screened the entire mtDNA sequence in 30 cases of human gastric cancer and matched normal tissues by using denaturing high-performance liquid chromatography (DHPLC) and DNA sequencing. Our data showed that high frequency (66.7%, 20÷30) of mitochondrial genome mutation occurred in gastric cancer. Among these variants, 17 cases (56.7%, 17÷30) were identified to be somatic mutation. High level mutant frequency was found inND4, ND5 coding genes and D-loop control region, which was 36.7%, 26.7% and 30% respectively. Comparing with complexes III, IV and Vof the electron transport chain, we found that variants appeared to be more frequent in the subunit genes of complex I. Most of mutations were base substitutions (85.4%, 41÷48). Our results suggested that mutations of subunit genes encoding complex I, especiallyND3, ND4 andND5 genes, might contribute to human gastric carcinogenesis.
基金
This work was supported by theNational Key Basic Science Research Program (Grant No. G1998051203)
the National Natural Science Foundation of China (Grant No. 39602526).
