Somatic mutations of the mitochondrial genome in human colorectal tumours

Kornelia Polyak, Yunbo Li, Hong Zhu, Christoph Lengauer, James K V Willson, Sanford D. Markowitz, Michael A. Trush, Kenneth W Kinzler, Bert Vogelstein

Research output: Contribution to journalArticle

Abstract

Alterations of oxidative phosphorylation in tumour cells were originally believed to have a causative role in cancerous growth. More recently, mitochondria have again received attention with regards to neoplasia, largely because of their role in apoptosis and other aspects of tumour biology. The mitochondrial genome is particularly susceptible to mutations because of the high level of reactive oxygen species (ROS) generation in this organelle, coupled with a low level of DNA repair. However, no detailed analysis of mitochondrial DNA in human tumours has yet been reported. In this study, we analysed the complete mtDNA genome of ten human colorectal cancer cell lines by sequencing and found mutations in seven (70%). The majority of mutations were transitions at purines, consistent with an ROS-related derivation. The mutations were somatic, and those evaluated occurred in the primary tumour from which the cell line was derived. Most of the mutations were homoplasmic, indicating that the mutant genome was dominant at the intracellular and intercellular levels. We showed that mitochondria can rapidly become homogeneous in colorectal cancer cells using cell fusions. These findings provide the first examples of homoplasmic mutations in the mtDNA of tumour cells and have potential implications for the abnormal metabolic and apoptotic processes in cancer.

Original languageEnglish (US)
Pages (from-to)291-293
Number of pages3
JournalNature Genetics
Volume20
Issue number3
DOIs
StatePublished - 1998

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Mitochondrial Genome
Colorectal Neoplasms
Mutation
Mitochondrial DNA
Neoplasms
Reactive Oxygen Species
Mitochondria
Purines
Cell Fusion
Oxidative Phosphorylation
Human Genome
Tumor Cell Line
DNA Repair
Organelles
Genome
Apoptosis
Cell Line
Growth

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Polyak, K., Li, Y., Zhu, H., Lengauer, C., Willson, J. K. V., Markowitz, S. D., ... Vogelstein, B. (1998). Somatic mutations of the mitochondrial genome in human colorectal tumours. Nature Genetics, 20(3), 291-293. https://doi.org/10.1038/3108

Somatic mutations of the mitochondrial genome in human colorectal tumours. / Polyak, Kornelia; Li, Yunbo; Zhu, Hong; Lengauer, Christoph; Willson, James K V; Markowitz, Sanford D.; Trush, Michael A.; Kinzler, Kenneth W; Vogelstein, Bert.

In: Nature Genetics, Vol. 20, No. 3, 1998, p. 291-293.

Research output: Contribution to journalArticle

Polyak, K, Li, Y, Zhu, H, Lengauer, C, Willson, JKV, Markowitz, SD, Trush, MA, Kinzler, KW & Vogelstein, B 1998, 'Somatic mutations of the mitochondrial genome in human colorectal tumours', Nature Genetics, vol. 20, no. 3, pp. 291-293. https://doi.org/10.1038/3108
Polyak K, Li Y, Zhu H, Lengauer C, Willson JKV, Markowitz SD et al. Somatic mutations of the mitochondrial genome in human colorectal tumours. Nature Genetics. 1998;20(3):291-293. https://doi.org/10.1038/3108
Polyak, Kornelia ; Li, Yunbo ; Zhu, Hong ; Lengauer, Christoph ; Willson, James K V ; Markowitz, Sanford D. ; Trush, Michael A. ; Kinzler, Kenneth W ; Vogelstein, Bert. / Somatic mutations of the mitochondrial genome in human colorectal tumours. In: Nature Genetics. 1998 ; Vol. 20, No. 3. pp. 291-293.
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