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Multiple Aberrations of Chromosome 3p Detected in Oral Premalignant Lesions

Authors' Affiliations: Departments of ¹ Cancer Genetics and Developmental Biology and ² Cancer Control Research, British Columbia Cancer Research Centre; and Departments of ³ Pathology and Laboratory Medicine, ⁴ Oral Biological and Medical Sciences, and ⁵ Computer Science, University of British Columbia, Vancouver, British Columbia, Canada

Requests for reprints: Ivy F.L. Tsui, British Columbia Cancer Research Centre, 675 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 1L3. Phone: 604-675-8111; Fax: 604-675-8283; E-mail: itsui{at}bccrc.ca.

The study of oral premalignant lesions (OPL) is crucial to the identification of initiating genetic events in oral cancer. However, these lesions are minute in size, making it a challenge to recover sufficient DNA from microdissected cells for comprehensive genomic analysis. As a step toward identifying genetic aberrations associated with oral cancer progression, we used tiling-path array comparative genomic hybridization to compare alterations on chromosome 3p for 71 OPLs against 23 oral squamous cell carcinomas. 3p was chosen because although it is frequently altered in oral cancers and has been associated with progression risk, its alteration status has only been evaluated at a small number of loci in OPLs. We identified six recurrent losses in this region that were shared between high-grade dysplasias and oral squamous cell carcinomas, including a 2.89-Mbp deletion spanning the FHIT gene (previously implicated in oral cancer progression). When the alteration status for these six regions was examined in 24 low-grade dysplasias with known progression outcome, we observed that they occurred at a significantly higher frequency in low-grade dysplasias that later progressed to later-stage disease (P < 0.003). Moreover, parallel analysis of all profiled tissues showed that the extent of overall genomic alteration at 3p increased with histologic stage. This first high-resolution analysis of chromosome arm 3p in OPLs represents a significant step toward predicting progression risk in early preinvasive disease and provides a keen example of how genomic instability escalates with progression to invasive cancer.

Key Words: oral premalignant lesions • chromosome 3p • array CGH

Commentary

Chromosomal Deletions and Progression of Premalignant Lesions: Less Is More

Ignacio I. Wistuba and Matthew Meyerson
Cancer Prevention Research 2008 1: 404-408. [Full Text] [PDF]