Vinmec Research Institute of Stem Cell and Gene Technology (VRSIG), 458 Minh Khai, Vinh Tuy, Hai Ba Trung, Hanoi, Viet Nam; Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH, 44106, USA.
Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH, 44106, USA.
J Genet Genomics. 2020 Jul 20;47(7):349-359. doi: 10.1016/j.jgg.2020.04.007. Epub 2020 Aug 1.
Mutations in the human mitochondrial genome have been observed in all types of human cancer, indicating that mutations might contribute to tumorigenesis, metastasis, recurrence, or drug response. This possibility is appealing because of the known shift from oxidative metabolism to glycolysis, known as the Warburg effect, that occurs in malignancy. Mitochondrial DNA (mtDNA) mutations could either be maternally inherited and predispose to cancer (germ line mutations) or occur sporadically in the mtDNA of specific tissues (tissue- or tumor-specific somatic mutations) and contribute to the tumor initiation and progression process. High-throughput sequencing technologies now enable comprehensive detection of mtDNA variation in tissues and bodily fluids, with the potential to be used as an early detection tool that may impact the treatment of cancer. Here, we discuss insights into the roles of mtDNA mutations in carcinogenesis, highlighting the complexities involved in the analysis and interpretation of mitochondrial genomic content, technical challenges in studying their contribution to pathogenesis, and the value of mtDNA mutations in developing early detection, diagnosis, prognosis, and therapeutic strategies for cancer.
人类线粒体基因组中的突变已在所有类型的人类癌症中被观察到，这表明突变可能有助于肿瘤发生、转移、复发或药物反应。这种可能性很有吸引力，因为众所周知，在恶性肿瘤中会发生从氧化代谢到糖酵解的转变，即众所周知的沃伯格效应。线粒体 DNA（mtDNA）突变要么是母系遗传并易患癌症（种系突变），要么在特定组织的 mtDNA 中随机发生（组织或肿瘤特异性体细胞突变），并有助于肿瘤的起始和进展过程。高通量测序技术现在可以全面检测组织和体液中的 mtDNA 变异，有可能作为一种早期检测工具，可能会影响癌症的治疗。在这里，我们讨论了 mtDNA 突变在致癌作用中的作用的见解，强调了分析和解释线粒体基因组内容所涉及的复杂性、研究其对发病机制的贡献的技术挑战以及 mtDNA 突变在开发早期检测、诊断、预后和癌症治疗策略方面的价值。
