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 x 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.
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