Mitochondrial mutations are a late event in the progression of head and neck squamous cell cancer.
OBJECTIVE
To determine the timing of mitochondrial mutations in the progression of head and neck squamous cell carcinoma.


METHODS
Twenty-three mitochondrial mutations were identified in 12 tumors using a high-throughput mitochondrial sequencing array. Areas of adjacent dysplastic and normal epithelium adjacent to tumors were sequenced using conventional methods for the presence of mutations that occurred in the corresponding tumor.


RESULTS
Two of 23 (8.7%) tumor mitochondrial mutations (2 of 12 tumors) were present in both the areas of adjacent dysplasia and normal epithelium. Five of 23 (21.7%) tumor mitochondrial mutations (4 of 12 tumors) were present in areas of adjacent dysplasia. Eleven of 12 tumors contained nonsynonymous mutations that resulted in protein coding alterations. A significant difference (P < 0.01, chi(2)) was found in the incidence of mitochondrial mutation that occurred after development of cancer compared with adjacent areas dysplasia and normal epithelium.


CONCLUSIONS
The majority of mitochondrial mutations occur during or after the transition of preneoplastic epithelium to cancer in head and neck squamous cell carcinoma, indicating that these are a late event in head and neck carcinogenesis.
Division of Plastic and Reconstructive Surgery, Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287-0910, USA.
Suhail K
SK
Mithani
Janis M
JM
Taube
Shaoyu
S
Zhou
Ian M
IM
Smith
Wayne M
WM
Koch
William H
WH
Westra
Joseph A
JA
Califano
D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D017931:DNA Primers / Q000737:chemistry; D004272:DNA, Mitochondrial / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis; D018450:Disease Progression; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D009154:Mutation; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000235:genetics*
D014408:Biomarkers, Tumor; D017931:DNA Primers; D004272:DNA, Mitochondrial; D004273:DNA, Neoplasm