Abstract | BACKGROUND: Somatic mutation in mitochondrial DNA ( mtDNA) has been proposed to contribute to initiation and progression of human cancer. In our previous study, high frequency of somatic mutations was found in the D-loop region of mtDNA of gastric cancers. However, it is unclear whether somatic mutations occur in the coding region of mtDNA of gastric cancers. METHODS: RESULTS: We identified eight somatic mutations in the coding region of mtDNAs of seven gastric cancer samples (7/31, 22.6%). Patients with somatic mutations in the entire mtDNA of gastric cancers did not show significant association with their clinicopathologic features. Among the eight somatic mutations, five point mutations (G3697A, G4996A, G9986A, C12405T and T13015C) are homoplasmic and three mutations (5895delC, 7472insC and 12418insA) are heteroplasmic. Four (4/8, 50%) of these somatic mutations result in amino acid substitutions in the highly conserved regions of mtDNA, which potentially lead to mitochondrial dysfunction. In addition, in vitro experiments in SC-M1 cells revealed that oligomycin-induced mitochondrial dysfunction promoted resistance to cisplatin and enhanced cell migration. N-acetyl cysteine was effective in the prevention of the oligomycin-enhanced migration, which suggests that reactive oxygen species generated by defective mitochondria may be involved in the enhanced migration of SC-M1 cells. GENERAL SIGNIFICANCE:
|
Authors | Wen-Yi Hung, Chew-Wun Wu, Pen-Hui Yin, Chun-Ju Chang, Anna Fen-Yau Li, Chin-Wen Chi, Yau-Huei Wei, Hsin-Chen Lee |
Journal | Biochimica et biophysica acta
(Biochim Biophys Acta)
Vol. 1800
Issue 3
Pg. 264-70
(Mar 2010)
ISSN: 0006-3002 [Print] Netherlands |
PMID | 19527772
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | Copyright (c) 2009 Elsevier B.V. All rights reserved. |
Chemical References |
- DNA Primers
- DNA, Mitochondrial
- DNA, Neoplasm
- Adenosine Triphosphate
|
Topics |
- Adenosine Triphosphate
(metabolism)
- Aged
- Amino Acid Substitution
- Cell Culture Techniques
(methods)
- Cell Movement
- DNA Primers
- DNA, Mitochondrial
(genetics)
- DNA, Neoplasm
(genetics)
- Disease Progression
- Female
- Genome, Mitochondrial
(genetics)
- Humans
- Male
- Middle Aged
- Mitochondria
(pathology, physiology)
- Mutation
- Oxygen Consumption
- Point Mutation
- Polymorphism, Single Nucleotide
- Sequence Deletion
- Stomach
(physiopathology)
- Stomach Neoplasms
(genetics, pathology)
|