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.

在所有类型的人类癌症中都观察到人类线粒体基因组的突变，这表明突变可能导致肿瘤发生、转移、复发或药物反应。这种可能性很有吸引力，因为已知从氧化代谢到糖酵解的转变，称为 Warburg 效应，发生在恶性肿瘤中。线粒体 DNA (mtDNA) 突变可能是母系遗传并易患癌症（生殖系突变），也可能偶尔发生在特定组织的 mtDNA 中（组织或肿瘤特异性体细胞突变），并有助于肿瘤的发生和进展过程。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，有可能用作可能影响癌症治疗的早期检测工具。