Mitochondrial DNA haplogroups and somatic mutations are associated with lung cancer in patients from Southwest China

Abstract

ABSTRACT. Mitochondrial DNA mutations play crucial roles in the pathogenesis and progression of human malignancies. Therefore, to determine whether maternal background or mitochondrial DNA somatic mutations were essential cofactors in the lung cancer of Chinese patients as well, the complete mitochondrial DNA displacement loop of the primary cancerous, matched para-cancerous normal and distant normal tissues for 79 Chinese patients with lung cancer were analyzed in this study. Our results indicated that the higher detected frequency of haplogroups prevalent in southern East Asia (53.16%; 42/79) versus those of northern East Asia in the studied population supported the southern East Asian characteristics of the Chinese lung cancer group. Further statistical analysis revealed that the haplogroups F* and G* contributed to the susceptibility to lung cancer in Chinese patients. In addition, by comparing sequences from different tissues of the same patients, a total of eight somatic mutations from six patients were detected. Combined with the fourteen somatic mutations identified in our previous study, the somatic mutation spectrum of the 79 Chinese patients with lung cancer was 25.32% (20/79). Our results suggest that mitochondrial DNA haplogroups and somatic mutations are associated with lung cancer in patients from Yunnan, Southwest China, and that somatic mitochondrial DNA mutations in the displacement loop can serve as potential biomarkers for clinical utility.

Mitochondrial dysfunction and potential anticancer therapy

“…Several studies indicated that both normal and cancer cells had equally high levels of heteroplasmy and no significant impact of mtDNA mutations have been observed in human individuals with thyroid, parathyroid, or adrenocortical carcinomas or glioblastoma . On the other hand, detected mtDNA mutations were correlated with head and neck squamous cell carcinoma (HNSCC), endometrial carcinoma (EC), in never smokers, and other lung cancer patients, as well as in individuals with bladder cancer, pituitary adenoma, breast, and skin cancers . Another factor mildly associating somatic mtDNA mutations with MDF is oxidative stress (OS) and some endogenous mechanisms responsible for mtDNA replication .…”

European mtDNA Variants Are Associated With Differential Responses to Cisplatin, an Anticancer Drug: Implications for Drug Resistance and Side Effects

“…Clinically, different ethnic populations show dissimilar susceptibilities to diseases and drug responses (8–10), and it has been suggested that mtDNA haplogroups may play important roles in these differences (11). Specific mtDNA haplogroups have also been associated with renal, prostate, breast, and lung cancers (12–15). In addition, somatic and germline mtDNA mutations, as well as levels of mtDNA copy numbers, have been associated with increased risk of cancer and different responses to anti-cancer drugs (16).…”

Is Malaysia’s banded langur, Presbytis femoralis femoralis, actually Presbytis neglectus neglectus? Taxonomic revision with new insights on the radiation history of the Presbytis species group in Southeast Asia

“…Thus, we intend to investigate the molecular systematics, population genetics, and biogeographic history of P. f. femoralis using the HVSI gene of mtDNA sequences to definitively solve the mystery. The properties of mtDNA, including their lack of recombination, fast evolutionary rate, maternal inheritance, higher copy number per cell, and higher population-specific polymorphisms, makes them distinct from nuclear DNAs and valuable genetic markers in population genetics study, especially primates (Smith et al 2007;Fang et al 2015;Akbar et al 2016). The HVSI region of mtDNA is primarily chosen because of datasets availability by Meyer et al (2011) for comparative analysis purposes and also this region has proven to be highly informative (Endicott and Ho 2008) and one of the three most variable regions in the D-loop of mtDNA (Malyarchuk et al 2002).…”