Multiple Aberrations of Chromosome 3p Detected in Oral Premalignant Lesions
Open Access
- 1 November 2008
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Prevention Research
- Vol. 1 (6), 424-429
- https://doi.org/10.1158/1940-6207.capr-08-0123
Abstract
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.Keywords
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This publication has 36 references indexed in Scilit:
- Inactivation of human mutL homolog 1 and mutS homolog 2 genes in head and neck squamous cell carcinoma tumors and leukoplakia samples by promoter hypermethylation and its relation with microsatellite instability phenotypeCancer, 2007
- TGFβ: the molecular Jekyll and Hyde of cancerNature Reviews Cancer, 2006
- Multiple Microalterations Detected at High Frequency in Oral CancerCancer Research, 2005
- Rare amplicons implicate frequent deregulation of cell fate specification pathways in oral squamous cell carcinomaOncogene, 2005
- Breakpoint identification and smoothing of array comparative genomic hybridization dataBioinformatics, 2004
- Epigenetic Profiling in Chronic Lymphocytic Leukemia Reveals Novel Methylation TargetsCancer Research, 2004
- RBSP3 (HYA22) is a tumor suppressor gene implicated in major epithelial malignanciesProceedings of the National Academy of Sciences of the United States of America, 2004
- Use of complete coverage array comparative genomic hybridization to define copy number alterations on chromosome 3p in oral squamous cell carcinomas.2003
- Differential deletions in 3p are associated with the development of head and neck squamous cell carcinoma in Indian patientsCancer Genetics and Cytogenetics, 2003
- A case-control study confirms that microsatellite assay can identify patients at risk of developing oral squamous cell carcinoma within a field of cancerization.2000