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Mutations in the D-loop region and increased copy number of mitochondrial DNA in human laryngeal squamous cell carcinoma

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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 χ2 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.

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Abbreviations

LSCC:

Laryngeal squamous cell carcinoma

mtDNA:

Mitochondrial DNA

HVI:

Hypervariable region I

HVII:

Hypervariable region II

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Acknowledgments

This work was supported by awards from National Science Foundation to Z.H. (#30973293); a Grant from Capital Development Fund for medical research to Z.H (#2007–2065).

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No potential conflicts of interest were disclosed.

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Authors and Affiliations

  1. 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

    Wei Guo, Hongbo Xu, Junwei Huang, Zheng Yang, Xiaohong Chen & Zhigang Huang

  2. Department Otolaryngology-Head and Neck Surgery, Beijing Fuxing Hospital, Capital Medical University, Beijing, 100730, China

    Denghua Yang

  3. Department Otolaryngology-Head and Neck Surgery, Fuxing Hospital, Capital Medical University, No. 20, Fuxingmenwai Avenue A, Xicheng District, Beijing, 100038, China

    Yang Zhang

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  1. Wei Guo
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  2. Denghua Yang
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  3. Hongbo Xu
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  4. Yang Zhang
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  5. Junwei Huang
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  6. Zheng Yang
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  7. Xiaohong Chen
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  8. Zhigang Huang
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Corresponding author

Correspondence to Zhigang Huang.

Additional information

Wei Guo, Denghua Yang contributed equally to this article.

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Guo, W., Yang, D., Xu, H. et al. Mutations in the D-loop region and increased copy number of mitochondrial DNA in human laryngeal squamous cell carcinoma. Mol Biol Rep 40, 13–20 (2013). https://doi.org/10.1007/s11033-012-1939-7

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  • DOI: https://doi.org/10.1007/s11033-012-1939-7

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