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.
Export Options
About this article
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 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Editorial [Hot Topic: Steroid Nuclear Receptor Family (Guest Editor: Pedro H.H. Hermkens)]
Current Medicinal Chemistry Rapid Non-genomic Vasodilator Actions of Oestrogens and Sex Steroids
Current Medicinal Chemistry Antibody-Drug Conjugate Targets
Current Cancer Drug Targets Induced Fit Docking and Automated QSAR Studies Reveal the ER-α Inhibitory Activity of <i>Cannabis sativa</i> in Breast Cancer
Recent Patents on Anti-Cancer Drug Discovery Bioengineering RNA Silencing Across the Life Kingdoms
Recent Patents on Biotechnology Nitrosative Stress as a Mediator of Apoptosis: Implications for Cancer Therapy
Current Pharmaceutical Design Inflammation and Antiangiogenesis in Cancer
Current Medicinal Chemistry Epigenetic Regulators Governing Cancer Stem Cells and Epithelial- Mesenchymal Transition in Oral Squamous Cell Carcinoma
Current Stem Cell Research & Therapy Modulation of Gene Transcription by Natural Products - A Viable Anticancer Strategy
Current Pharmaceutical Design Targeting Histone Onco- Modifications Using Plant-Derived Products
Current Drug Targets Chemoprevention with Phytonutrients and Microalgae Products in Chronic Inflammation and Colon Cancer
Current Pharmaceutical Design Safety of Systemic Biologic Agents in the Treatment of Non-malignant Skin Disorders
Current Drug Safety Developing Histone Deacetylase Inhibitors as Anti-Cancer Therapeutics
Current Medicinal Chemistry Low Grade Inflammation as a Common Pathogenetic Denominator in Age-Related Diseases: Novel Drug Targets for Anti-Ageing Strategies and Successful Ageing Achievement
Current Pharmaceutical Design The Role of Diabetes in Molecular Pathogenesis of Cancer
Current Signal Transduction Therapy Carbonic Anhydrase Inhibitors and the Management of Cancer
Current Topics in Medicinal Chemistry Synthesis and Biological Activity of 3-N-Substituted Estrogen Derivatives as Breast Cancer Agents
Mini-Reviews in Medicinal Chemistry An Overview on Keratinocyte Growth Factor: From the Molecular Properties to Clinical Applications
Protein & Peptide Letters Transcription Factors as Targets for Cancer Therapy: AP-1 a Potential Therapeutic Target
Current Cancer Therapy Reviews Biomarkers for Systemic Therapy in Ovarian Cancer
Current Cancer Drug Targets