Profiling of genomic alterations of mitochondrial DNA in gingivobuccal oral squamous cell carcinoma: Implications for disease progress

Mitochondrion. 2019 May:46:361-369. doi: 10.1016/j.mito.2018.09.006. Epub 2018 Sep 24.

Abstract

We have identified 164 somatic mutations in mitochondrial DNA in gingivobuccal oral cancer by deep sequencing the mitochondrial genome from paired tumor and blood DNA samples from 89 patients. We have found evidence of positive selection of somatic nonsynonymous mutations. Non-synonymous mutations in mitochondrial respiratory genes were found to increase the risk of lymph node metastasis (P = 0.0028). We have observed a significant reduction in mitochondrial DNA copy number in tumor DNA of these patients compared to the DNA from adjacent normal tissue samples (P < 1 × 10-6). Analysis of transcriptome data of tumor and adjacent normal tissue revealed patients harboring mutations in mitochondrial protein-coding genes exhibited reduced expression of mitochondrial transcripts.

Keywords: Gingivobuccal Oral Squamous Cell Carcinoma; Lymph node metastasis; Massively parallel sequencing; Mitochondrial DNA; Mitochondrial respiratory complex genes; Somatic mutation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology*
  • DNA, Mitochondrial / genetics*
  • Disease Progression
  • Female
  • Gene Expression Profiling
  • Genetic Predisposition to Disease*
  • Genetic Variation*
  • Gingival Neoplasms / genetics*
  • Gingival Neoplasms / pathology*
  • Humans
  • Male
  • Middle Aged
  • Mutation, Missense
  • Prognosis

Substances

  • DNA, Mitochondrial