title: Mutations in the D-loop region and increased copy number of mitochondrial DNA in human laryngeal squamous cell carcinoma.
abstract: The effects of D-loop mutations and the mtDNA copy number alterations in LSCC are poorly understood. Herein, we investigated the features and roles of somatic mutations of the D-loop region and copy number alterations in mtDNA of LSCC. Using direct sequencing and real-time quantitative PCR, we examined D-loop mutations and mtDNA copy number in LSCC tissues, paracancerous normal tissues and peripheral vein blood samples from 40 LSCC patients. A student's t test, ANOVA test and χ(2) test were used to analyze association among mutations, mtDNA copy number alterations with clinicopathologic parameters. The results revealed that 21 tumors (52.5 %) had somatic mtDNA D-loop mutations with a total of 34 mutations. Among them, 28 (82.4 %) and 6 (17.6 %) were located in HVII and HVI, respectively. D-loop mutations correlated with tumor differentiation and p53 mutation (P < 0.05), and increased mtDNA copy number. In addition, mtDNA copy number in tumor tissues and paracancerous normal tissues were all significantly higher than in peripheral blood (P < 0.05). The copy number of mtDNA in the cases which carried D-loop mutation was significantly higher than that of the negative cases (P < 0.05). These results suggest that the mtDNA D-loop in LSCC is an unstable region with a high frequency of somatic mutation and polymorphisms. Together with the increase in mtDNA copy number, these factors may play a role in carcinogenesis of the larynx.
authors.affiliation: Key Laboratory of Otolaryngology Head and Neck Surgery, Department of Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, No. 1, Dong Jiao Min Xiang, Eastern District Beijing, Beijing 100730, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.forename: Denghua
authors.initials: D
authors.lastname: Yang
authors.forename: Hongbo
authors.initials: H
authors.lastname: Xu
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Junwei
authors.initials: J
authors.lastname: Huang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yang
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Chen
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Huang
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D009154:Mutation; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: D004272:DNA, Mitochondrial