Differential expression profiling of oral squamous cell carcinoma identifies the involvement of a major signaling pathway. S. Chakraborty¹, S.M.A. Mohiyuddin², K.S. Gopinath³, A. Kumar¹. 1) MRDG, Indian Institute of Science, Bangalore, Karnataka, India; 2) RL Jalappa Hospital and Research Centre, Kolar, India; 3) Bangalore Institute of Oncology, Bangalore, India.
   Oral squamous cell carcinoma (oral cancer) accounts for almost 40% of all cancers in India. Despite rapid advancement in therapeutic strategies, its low five-year survival period remains unchanged in the past two decades. Thus, finding a biological tumor marker to increase the early diagnosis and treatment monitoring rates is of paramount importance. To elucidate the molecular alterations underlying oral cancer, we employed the DDRT-PCR technique. Our DDRT-PCR profiling showed 51 fragments (cDNAs) that were differentially regulated. Of these, 27 fragments were confirmed as true differentials by reverse Northern analysis. Eight of the genes have been validated by RT-PCR in a panel of 16 matched normal and tumor patient samples and show potential as future therapeutic targets. One of the genes identified by DDRT-PCR has been shown to interact with another tumor suppressor gene which is an important regulator of a major signaling pathway. Investigation of the mechanism of downregulation of this tumor suppressor gene, which we observed in patient samples, led to the detection of loss of heterozygosity at the gene locus. Analysis of some of the key players of this pathway by RT-PCR revealed aberrant gene expression patterns. Hyperphoshorylation of some of the kinases in this pathway in oral tumors also indicated its constitutive activation. Probing the oral transcriptome by DDRT-PCR has identified some interesting genes not associated with oral cancers earlier. Our initial results seem to implicate the involvement of a major signaling pathway that may play a role in triggering the onset or progression of a subset of cancers of the oral cavity for the first time. The results will be presented and discussed (Financially supported by DBT and CSIR, New Delhi).