title: Mitochondrial DNA quantity increases with histopathologic grade in premalignant and malignant head and neck lesions.
abstract: OBJECTIVE
  Mitochondria are highly susceptible to oxidative damage. Although mitochondrial function decreases with oxidative damage, overall mitochondrial DNA (mtDNA) content increases to compensate for general mitochondrial dysfunction. We performed quantitative polymerase chain reaction for genes specific to mitochondrial and nuclear genomes to investigate relative mitochondrial abundance in a spectrum of dysplastic head and neck lesions.
  
  
  METHODS
  DNA from mild, moderate, and severe dysplasias, as well as invasive tumors and normal mucosal cells, was extracted. Using quantitative polymerase chain reaction, mitochondrial to nuclear DNA ratios were determined by quantification of cytochrome c oxidase subunit 1 (CoxI) and beta-actin genes.
  
  
  RESULTS
  Mean CoxI/beta-actin DNA ratios for mild, moderate, and severe premalignant lesions were 0.0529, 0.0607, and 0.1021, respectively. The mean ratio for the normal mucosal cells contained in saliva was 0.0537, whereas the mean ratio for tumors was 0.1667. As a whole, our experimental model demonstrated significance (P = 0.0358). Comparisons between individual categories showed borderline significance when compared with the normal group, with P values of 0.0673, 0.0747, and 0.0824 for moderate and severe dysplasia and invasive tumor, respectively.
  
  
  CONCLUSIONS
  Head and neck squamous cell carcinomas arise through premalignant intermediates and may be merely morphologic manifestations of accumulated genetic alterations. In keeping with this molecular tumor progression model, our study shows that mtDNA increases according to histopathologic grade, a phenomenon that may be a feedback mechanism that compensates for a generalized decline in respiratory chain function. Therefore, high mtDNA content may be another marker of genetic alteration, a measure of relative DNA injury, and a surrogate measure of histopathologic grade.
authors.affiliation: Head and Neck Cancer Research Division, Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287-0910, USA.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Kim
authors.forename: John D
authors.initials: JD
authors.lastname: Clinger
authors.forename: Brett G
authors.initials: BG
authors.lastname: Masayesva
authors.forename: Patrick K
authors.initials: PK
authors.lastname: Ha
authors.forename: Marianna L
authors.initials: ML
authors.lastname: Zahurak
authors.forename: William H
authors.initials: WH
authors.lastname: Westra
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Califano
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D004247:DNA / Q000032:analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000235:genetics*; D012463:Saliva / Q000737:chemistry
chemical_list: D014408:Biomarkers, Tumor; D004272:DNA, Mitochondrial; D004247:DNA