Abstract
As mitochondria participate in fundamental process of the cellular metabolism, recent research has addressed the role of mitochondria, and of mitochondrial DNA (mtDNA), in apoptosis, aging, and complex diseases. The association between mtDNA and cancer has been discussed since the beginning of the last century, and more recently, it has gained attention due to the observation of many somatic mutations in several types of cancers. In this review we describe those germinal mutations that have been associated to cancer, and present a compilation of somatic mutations that have been observed in different cancer tissues, describing relevant characteristics among them in a phylogenetic context. We also summarize the drawbacks and criticisms made towards the studies that report an association between mtDNA mutations and cancer, and discuss the experimental models used to analyse this relationship. Although many reported somatic mutations may actually be the outcome of laboratory artefacts, a considerable number could be authentic and may have a relationship with cancer development. In our compilation, we have observed 271 cancer mutations occurring in conserved positions of mtDNA, 70 of them appearing in more than one tumour. These mutations may be candidates to be used as cancer biomarkers, and deserve further investigation, perhaps through the use of experimental models and by an analysis of tumours of distinct grade to determine if the mutations arose early during tumourigenesis. Experiments with cybrids have been successfully used; however, models are needed in which specific mtDNA variants may be introduced into the same mitochondrial and cellular background.
Keywords: Mitochondrial DNA, cancer, warburg effect, somatic mutations, cybrids
Current Topics in Medicinal Chemistry
Title: Mitochondrial DNA Mutations in Cancer: A Review
Volume: 8 Issue: 15
Author(s): Cristina Santos, Moviea Martinez, Manvela Lima, You-Jin Hao, Nelson Simoes, Rafeal Montiel, Monica Martinez and Manuela Lima
Affiliation:
Keywords: Mitochondrial DNA, cancer, warburg effect, somatic mutations, cybrids
Abstract: As mitochondria participate in fundamental process of the cellular metabolism, recent research has addressed the role of mitochondria, and of mitochondrial DNA (mtDNA), in apoptosis, aging, and complex diseases. The association between mtDNA and cancer has been discussed since the beginning of the last century, and more recently, it has gained attention due to the observation of many somatic mutations in several types of cancers. In this review we describe those germinal mutations that have been associated to cancer, and present a compilation of somatic mutations that have been observed in different cancer tissues, describing relevant characteristics among them in a phylogenetic context. We also summarize the drawbacks and criticisms made towards the studies that report an association between mtDNA mutations and cancer, and discuss the experimental models used to analyse this relationship. Although many reported somatic mutations may actually be the outcome of laboratory artefacts, a considerable number could be authentic and may have a relationship with cancer development. In our compilation, we have observed 271 cancer mutations occurring in conserved positions of mtDNA, 70 of them appearing in more than one tumour. These mutations may be candidates to be used as cancer biomarkers, and deserve further investigation, perhaps through the use of experimental models and by an analysis of tumours of distinct grade to determine if the mutations arose early during tumourigenesis. Experiments with cybrids have been successfully used; however, models are needed in which specific mtDNA variants may be introduced into the same mitochondrial and cellular background.
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Cite this article as:
Santos Cristina, Martinez Moviea, Lima Manvela, Hao You-Jin, Simoes Nelson, Montiel Rafeal, Martinez Monica and Lima Manuela, Mitochondrial DNA Mutations in Cancer: A Review, Current Topics in Medicinal Chemistry 2008; 8 (15) . https://dx.doi.org/10.2174/156802608786141151
DOI https://dx.doi.org/10.2174/156802608786141151 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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