Somatic Mitochondrial DNA Mutations in Oral Cancer of Betel Quid Chewers

Abstract

Somatic mitochondrial DNA alteration is a general phenomenon that occurs in cancerous cells. Although numerous mtDNA mutations have been identified in various tumors, the pathogenic significance of these mutations remains unclear. In order to better understand the role of mtDNA mutations in the neoplastic process of oral cancer, the occurrence of mtDNA mutations in oral squamous cell carcinomas was screened by temporal temperature gradient gel electrophoresis (TTGE). The entire mitochondrial genome was amplified with 32 pairs of overlapping primers. The DNA fragments showing different banding patterns between normal and tumor mtDNA were sequenced for the identification of the mutations. Fourteen of 18 (77.8%) tumors had somatic mtDNA mutations with a total of 26 mutations. Among them, 6 were in mRNA coding region. Three were missense mutations (C14F, H186R, T173P) in NADH dehydrogenase subunit 2 (ND2). One frameshift mutation, 9485delC, was in cytochrome c oxidase subunit III. Eight (44%) tumors had insertion or deletion mutations in the np303‐309 poly C region of the D‐loop. Our results demonstrate that somatic mtDNA mutations occur in oral cancer. The missense and frameshift mutations in the evolutionary conserved regions of the mitochondrial genome may have functional significance in the pathogenesis of oral cancer.

Prevalence of promoter mutations in the TERT gene in oral cavity squamous cell carcinoma

“…Previously, Tan et al demonstrated that somatic mitochondrial DNA mutations occur in oral cancer with a history of betel quid chewing. Fourteen of 18 oral cavity SCC tumors (77.8%) had somatic mitochondrial DNA mutations with a total of 26 mutations.…”

“…Fourteen of 18 oral cavity SCC tumors (77.8%) had somatic mitochondrial DNA mutations with a total of 26 mutations. Among them, 5 mutations were a cytidine‐to‐thymidine transition, and this type of mutation is similar to that induced by UV exposure . Furthermore, Hsieh et al analyzed the conserved regions of the p53 gene in 187 oral cavity SCC tumor specimens with various exposure histories of betel nut chewing, smoking, and alcohol drinking.…”

Evidence for frequent and tissue-specific sequence heteroplasmy in human mitochondrial DNA

“…Interestingly, 740 the 71d LHP was also found in samples of oral cancer of individuals 741 chewing betel quid (Tan et al, 2004). …”

Mitochondrial NADH dehydrogenase polymorphisms are associated with breast cancer in Poland

“…That mutation caused replacement of threonine with alanine. In the cells of intestinal crypts (Taylor et al 2003) and in the case of oral cancer – by proline (Tan et al 2004). …”