Mitochondrial resequencing arrays detect tumor-specific mutations in salivary rinses of patients with head and neck cancer

Suhail K. Mithani, Ian M. Smith, Shaoyu Zhou, Andrew Gray, Wayne Martin Koch, Anirban Maitra, Joseph A. Califano

Research output: Contribution to journalArticle

Abstract

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 MitoChipv 2.0 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.

Original languageEnglish (US)
Pages (from-to)7335-7340
Number of pages6
JournalClinical Cancer Research
Volume13
Issue number24
DOIs
StatePublished - Dec 15 2007

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Head and Neck Neoplasms
Mitochondrial DNA
Mutation
Neoplasms
Mitochondrial Genome
Population
Mitochondrial Diseases
DNA
DNA Probes
Body Fluids
Carcinoma, squamous cell of head and neck
Research Design
Cell Line

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Mitochondrial resequencing arrays detect tumor-specific mutations in salivary rinses of patients with head and neck cancer. / Mithani, Suhail K.; Smith, Ian M.; Zhou, Shaoyu; Gray, Andrew; Koch, Wayne Martin; Maitra, Anirban; Califano, Joseph A.

In: Clinical Cancer Research, Vol. 13, No. 24, 15.12.2007, p. 7335-7340.

Research output: Contribution to journalArticle

Mithani, Suhail K. ; Smith, Ian M. ; Zhou, Shaoyu ; Gray, Andrew ; Koch, Wayne Martin ; Maitra, Anirban ; Califano, Joseph A. / Mitochondrial resequencing arrays detect tumor-specific mutations in salivary rinses of patients with head and neck cancer. In: Clinical Cancer Research. 2007 ; Vol. 13, No. 24. pp. 7335-7340.
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abstract = "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 MitoChipv 2.0 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.",
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AU - Koch, Wayne Martin

AU - Maitra, Anirban

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N2 - 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 MitoChipv 2.0 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.

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