m.6267G>A: a recurrent mutation in the human mitochondrial DNA that reduces cytochrome c oxidase activity and is associated with tumors

Complete sequencing of the mitochondrial genome of 13 cell lines derived from a variety of human cancers revealed nine novel mitochondrial DNA (mtDNA) variations. One of them, m.6267G>A, is a recurrent mutation that introduces the Ala122Thr substitution in the mitochondrially encoded cytochrome c...

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Bibliographic Details
Published in:Human mutation 2006-06, Vol.27 (6), p.575-582
Main Authors: Gallardo, M. Esther, Moreno-Loshuertos, Raquel, López, Celia, Casqueiro, Mercedes, Silva, Javier, Bonilla, Felix, de Córdoba, Santiago Rodríguez, Enríquez, José Antonio
Format: Article
Language:English
Subjects:
Amino Acid Sequence
cancer
Cell Line, Tumor
Conserved Sequence
COX
Culture Media
DNA Mutational Analysis
DNA, Mitochondrial - genetics
Electron Transport Complex IV - chemistry
Electron Transport Complex IV - genetics
Electron Transport Complex IV - metabolism
Galactose - pharmacology
Humans
mitochondrial DNA
Molecular Sequence Data
mtDNA
Neoplasms - enzymology
Neoplasms - genetics
OXPHOS
Oxygen Consumption
Polymorphism, Restriction Fragment Length
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Summary:Complete sequencing of the mitochondrial genome of 13 cell lines derived from a variety of human cancers revealed nine novel mitochondrial DNA (mtDNA) variations. One of them, m.6267G>A, is a recurrent mutation that introduces the Ala122Thr substitution in the mitochondrially encoded cytochrome c oxidase I (MT‐CO1): p.MT‐CO1: Ala122Thr (GenBank: NP_536845.1). Biochemical analysis of the original cell lines and the transmitochondrial cybrids generated by transferring mitochondrial DNAs to a common nuclear background, indicate that cytochrome c oxidase (COX) activity, respiration, and growth in galactose are impaired by the m.6267G>A mutation. This mutation, found twice in the cancer cell lines included in this study, has been also encountered in one out of 63 breast cancer samples, one out of 64 colon cancer samples, one out of 260 prostate cancer samples, and in one out of 15 pancreatic cancer cell lines. In all instances the m.6267G>A mutation was associated to different mtDNA haplogroups. These findings, contrast with the extremely low frequency of the m.6267G>A mutation in the normal population (1:2264) and its apparent absence in other pathologies, strongly suggesting that the m.6267G>A missense mutation is a recurrent mutation specifically associated with cancer. Hum Mutat 27(6), 575–582, 2006. © 2006 Wiley‐Liss, Inc.
ISSN:1059-7794
1098-1004
DOI:10.1002/humu.20338