title: Mitochondrial DNA mutation in normal margins and tumors of recurrent head and neck squamous cell carcinoma patients.
abstract: Mitochondrial DNA (mtDNA) mutations were reported in primary head and neck squamous cell carcinoma (HNSCC) patients. However, very little information is available on the mtDNA mutation pattern in the histologically negative surgical margins and tumors of HNSCC patients who experienced tumor recurrence. The present study aimed at understanding the nature and timing of mtDNA mutation in histologically negative margins, and tumors in HNSCC patients who developed local recurrence during the follow-ups. The entire 16.5-kb mitochondrial genome was sequenced in matched normal lymphocytes, histologically normal margins, and tumors of 50 recurrent HNSCC patients. The mtDNA mutations were then compared with clinical parameters. Forty-eight percent (24 of 50) of patients harbored at least one somatic mtDNA mutation in the tumor, and a total of 37 somatic mtDNA mutations were detected. The mtDNA mutations were mostly heteroplasmic in nature and nucleotide transitions (A<-->G; T<-->C). Forty-six percent of the mutations (17 of 37) were detected in the tumors and were also detectable in the corresponding histologically normal margin of the patients. The mtDNA mutations involved both coding and noncoding regions of the mtDNA. The majority (9 of 17, 53%) of the noncoding mutations involved tRNAs. Seventy-five percent (15 of 20) of the coding mtDNA mutations were nonsynonymous in nature and mainly affected cytochrome c oxidase (Complex IV), frequently altered in different human mitochondrial diseases including cancer. Analysis of mtDNA mutation could be an invaluable tool for molecular assessment of histologically negative margins and as well for monitoring HNSCC patients with locoregional recurrences.
authors.affiliation: Department of Otolaryngology, Johns Hopkins University School of Medicine, 601 North Caroline Street, JHOC 6221, Baltimore, MD 21287, USA.
authors.forename: Santanu
authors.initials: S
authors.lastname: Dasgupta
authors.forename: Rachel
authors.initials: R
authors.lastname: Koch
authors.forename: William H
authors.initials: WH
authors.lastname: Westra
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Califano
authors.forename: Patrick K
authors.initials: PK
authors.lastname: Ha
authors.forename: David
authors.initials: D
authors.lastname: Sidransky
authors.forename: Wayne M
authors.initials: WM
authors.lastname: Koch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000032:analysis / Q000235:genetics*; D054629:Genome, Mitochondrial; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D006262:Health; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis
chemical_list: D004272:DNA, Mitochondrial