ABSTRACT
ABSTRACT Biomarkers are used in cancer detection, diagnosis, and prognosis. In cancer, most genetic markers are based on nuclear DNA; mitochondrial DNA (mtDNA) has not been utilized very extensively. This article provides information about using mtDNA alterations as biomarkers to detect different tumor types at early stages of carcinogenesis. Mitochondria play an important role in cellular energy metabolism, free radical generation, and apoptosis. Alterations in respiratory activity and mtDNA alterations are an integral part of carcinogenesis. Mitochondria contain their own genome along with their own transcription, translation, and protein assembly machinery. Because mtDNA lacks introns,
Abbreviations ........................................................................................................................................... 96 6.1 Introduction .................................................................................................................................... 96 6.2 Why Mitochondrial DNA Markers? .............................................................................................. 96 6.3 Mitochondrial DNA in Different Cancers ..................................................................................... 98
6.3.1 Bladder Cancer .................................................................................................................. 98 6.3.2 Brain Cancer ...................................................................................................................... 99 6.3.3 Breast Cancer..................................................................................................................... 99 6.3.4 Colon Cancer ..................................................................................................................... 99 6.3.5 Endometrial Cancer ......................................................................................................... 100 6.3.6 Esophageal Cancer .......................................................................................................... 100 6.3.7 Gastric Cancer ................................................................................................................. 100 6.3.8 Head and Neck Cancer .....................................................................................................101 6.3.9 Kidney Cancer ..................................................................................................................101 6.3.10 Leukemia ..........................................................................................................................101 6.3.11 Liver Cancer .....................................................................................................................101 6.3.12 Lung Cancer .................................................................................................................... 102 6.3.13 Oral Cancer ..................................................................................................................... 102 6.3.14 Ovarian Cancer ................................................................................................................ 102 6.3.15 Pancreatic Cancer ............................................................................................................ 102 6.3.16 Prostate Cancer ................................................................................................................ 103 6.3.17 Skin Cancer ..................................................................................................................... 103 6.3.18 Thyroid Cancer ................................................................................................................ 103
6.4 Types of Samples Suitable for Isolating mtDNA and Mutation Analysis ................................... 104 6.5 Technological Advancements ...................................................................................................... 105 6.6 Haplogroups in Mitochondria ...................................................................................................... 105 6.7 Analytical and Clinical Validation of Mitochondrial Biomarkers .............................................. 106 6.8 Concluding Remarks and Future Perspectives ............................................................................ 107 Acknowledgment ................................................................................................................................... 108 References .............................................................................................................................................. 109
it does not have histones and is more susceptible to oxidative damage and other environmental insults. It has been suggested that most mutations and deletions will occur in coding sequences, and the subsequent accumulation of mutations may lead to tumor formation. Mitochondrial mutations have been reported in bladder, brain, breast, colon, cervical, esophageal, gastric, liver, lung, and prostate cancers. Some of these mutations occur quite early during cancer development and can be used in screening large populations to identify high-risk individuals. Mitochondrial DNA alteration can be detected in biospecimens collected non-invasively. The implications of using mitochondrial information in identifying populations that are at high risk of developing cancer are discussed.
