In preliminary progression model of head and neck squamous cell carcinoma (HNSCC), deletions in multiple chromosomal regions were suggested to be associated with the development of premalignant lesions of head and neck. Among these regions, deletion in 9p21 with hyperplastic lesions and deletions in the 3p12.3, 3p21.31, 3p22.1, 9p21-22, 9q22.3 and 11q22.3- 24 regions with the mild dysplastic lesions have been seen. Multiple candidate genes e.g. ROBO1/2, CDC25A, LIMD1, RBSP3, SH3GL2, p16 etc were located in these chromosomal regions that showed differential alterations during the development of premalignant lesions. In addition, EGFR over expression in hyperplastic lesions and inactivation of p53 in mild dysplastic lesions have been seen. These genes regulate different cellular pathways like cell cycle, EGFR signaling, ROBO1 signaling etc. It was evident that the alterations of these genes were not analyzed in the same set of samples to understand the actual sequence of genetic events associated with the development of premalignant lesions of head and neck. Among the pathways associated with the development of HNSCC, the molecular mechanism of EGFR over expression and inactivation of ROBO1 signaling were not analyzed in detail. Thus, in this study attempts have been made first to find out the sequence of the genetic events associated with the development of pre-malignant lesions; then the molecular mechanism of EGFR over expression and inactivation of ROBO1 signaling were analyzed to understand the molecular pregression of premalignant lesions.
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