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Mitochondrial Resequencing Arrays Detect Tumor-Specific Mutations in Salivary Rinses of Patients with Head and Neck Cancer

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

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

Purpose: Alterations of the mitochondrial genome have been identified in multiple solid tumors and in many head and neck squamous cell carcinomas (HNSCC). Identification of mitochondrial mutations in the salivary rinses of patients with HNSCC has potential application in disease detection. In this study, we used the MitoChip v2.0 mitochondrial genome resequencing array to detect minor populations of mitochondrial DNA in salivary rinses of patients with HNSCC.

Experimental Design: Salivary rinses from 13 patients with HNSCC, whose tumors carried mitochondrial mutations, were collected before surgical resection. DNA isolated from salivary rinses and serial dilutions of DNA derived from HNSCC-derived cell lines with known mitochondrial mutations were sequenced using the MitoChip, and analyzed using a quantitative algorithm which we developed to detect minor populations of mitochondrial DNA from MitoChip probe intensity data.

Results: We detected heteroplasmic populations of mitochondrial DNA up to a 1:200 dilution using MitoChip v2.0 and our analysis algorithm. A logarithmic relationship between the magnitude of assay intensity and concentration of minor mitochondrial populations was shown. This technique was able to identify tumor-specific mitochondrial mutations in salivary rinses from 10 of 13 (76.9%) patients with head and neck cancer.

Conclusions: Minor populations of mitochondrial DNA and disease-specific mitochondrial mutations in salivary rinses of patients with HNSCC can be successfully identified using the MitoChip resequencing array and the algorithm which we have developed. This technique has potential application in the surveillance of patients after resection and may have applicability in the surveillance of body fluids in other tumor types.