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Mitochondrial Mutations Are a Late Event in the Progression of Head and Neck Squamous Cell Cancer

Authors' Affiliations: ¹ Division of Plastic and Reconstructive Surgery, Department of Surgery, ² Department of Pathology, and ³ Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland

Requests for reprints: Joseph A. Califano, Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, 601 North Caroline Street, 6th Floor, Baltimore, MD 21287-0910. Phone: 410-502-5153; E-mail: jcalifa{at}jhmi.edu.

Purpose: To determine the timing of mitochondrial mutations in the progression of head and neck squamous cell carcinoma.

Experimental Design: 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, 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.

Commentary

A Disturbance in the Force—Mitochondrial Mutations in Squamous Cell Carcinoma of the Head and Neck

Ezra E.W. Cohen
Clin. Cancer Res. 2007 13: 4317-4319. [Full Text] [PDF]