Early detection of cancer of the mouth and throat (head and neck squamous cell carcinoma [HNSCC]) wouldresult in substantial improvement in survival for the 40,000 Americans diagnosed with this disease each yearwhile reducing morbidity associated with treatment, Changes in DNA that underly tumorigenesis are idealmolecular markers for highly sensitive and specific approaches to early detection. We have had promisingresults in pilot projects for detection of HNSCC in oral rinses (saliva) and serum of affected individuals usinghypermethylation markers identified during the first funding period by Project 1. In the proposed new fundingperiod, it is anticipated that the number of promising markers identified in Project 1 will double or triple . Inorder to produce an accurate, useful and cost-effective detection test, it will be necessary to combinemarkers that have shown initial promise into detection panels. However, the presence of some markers insaliva and serum of healthy control subjects requires that detection panels be compartment specific.We willassemble and verify candidate markers and panels through the assessment of tumor-specifichypermethylation of promoter regions in tumors, premalignant lesions, exfoliated cells in oral rinsespecimens, and serum. Quantitative methylations specific PCR which is amenable to high-throughputapplication will be employed. The prevelance of alterations in sets of tumors will be assessed, followed byevaluation of the presence of identical markers in clinical specimens (saliva and serum). Simple sensitivityand specificity estimates will be explored in various panel combinations. The proposed panels of markerswillthen be tested in samples from subjects enrolled in premalignant and post-treatment surveillance studies(aims 2 and 3). Subjects will be recruited at the Johns Hopkins Medical Institutions and the MD AndersonCancer Center. The utility of marker panels for detection and prediction of recurrence/progression will beexplored.
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