Mitochondrial C-tract alteration in premalignant lesions of the head and neck: A marker for progression and clonal proliferation

Patrick K. Ha, Betty C. Tong, William H. Westra, Montserrat Sanchez-Cespedes, Paola Parrella, Marianna Zahurak, David Sidransky, Joseph A. Califano

Research output: Contribution to journalArticlepeer-review

97 Scopus citations


Purpose: Although mitochondrial DNA mutations have been described recently in many different tumor types, the nature and timing of such alterations remain unclear. In an effort to further examine the role of mitochondrial DNA mutations in carcinogenesis, we examined 137 premalignant lesions of the head and neck from 93 patients for DNA alterations in the poly-cytosine tract (C-tract) of the displacement loop, discovered recently to be a hot spot of mitochondrial DNA alteration. Experimental Design: All premalignant lesions were tested using a length-based PCR assay, which amplified the C-tract region of mitochondrial DNA. Somatic microsatellites at six loci were also tested on a subset of patients with metachronous or synchronous lesions found to possess a mitochondrial C-tract alteration. Results: Thirty-four of 93 (37%) patients harbored lesions that displayed a C-tract alteration. There was a clear increase in incidence from histologically benign hyperplasia (22%) to squamous carcinoma in situ (62%: P < 0.01). We also tested synchronous dysplastic lesions, metachronous dysplastic lesions, and normal epithelium adjacent to dysplastic epithelium with this assay. In most cases, the mitochondrial C-tract status identified a clonal relationship between these lesions. Genomic microsatellites also confirmed that a clonal relationship was present in many of these cases. Conclusions: Mitochondrial DNA alterations in the head and neck occur in the earliest premalignant lesions and demonstrate a rising incidence that parallels histological severity. These alterations are valuable as additional markers of histopathological progression.

Original languageEnglish (US)
Pages (from-to)2260-2265
Number of pages6
JournalClinical Cancer Research
Issue number7
StatePublished - Jan 1 2002

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


Dive into the research topics of 'Mitochondrial C-tract alteration in premalignant lesions of the head and neck: A marker for progression and clonal proliferation'. Together they form a unique fingerprint.

Cite this