The study of oral premalignant lesions (OPLs) 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 (CGH) to compare alterations on chromosome 3p for 71 OPLs 
against 23 oral squamous cell carcinomas (OSCCs).  3p was chosen because, while 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 (HGDs) and OSCCs, 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 (LGDs) with 
known progression outcome, we observed that they occurred at a significantly higher 
frequency in LGDs 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 histological stage.  This first 
high resolution analysis of chromosome arm 3p in oral premalignant lesions 
represents a significant step towards predicting progression risk in early 
pre-invasive disease and provides a keen example of how genomic instability 
escalates with progression to invasive cancer.