Squamous cell carcinoma (SCC) affects 60,000 persons each year in the United States. SCC of the Head and Neck (SCCHN) accounts for 10 percent of all cancers and 5 percent of all cancer deaths. Useful biomarkers of prognosis and subgrouping have been elusive for this tumor type. Most deletions result in loss of tumor suppressor and other tumor-associated genes. Genetic losses are common at multiple specific sites in SCCHN tumors. Preliminary studies have identified the regions that are most often lost in SCC, and have demonstrated the presence of mitotic instability in about 7 percent of tumors, as has been associated with a highly mutable tumor phenotype in some other cancers. These studies also indicate an association between loss or instability and decreased survival. A central objective of this proposal is to determine which genetic changes, in the 8 regions that are most commonly lost in SCCHN (5q, 8p, 9p, 10p, 18q, 21q and two regions within 3p), have biological significance in the progression of the disease, and which add prognostic accuracy after considering known parameters of clinical importance such as anatomic site, smoking and alcohol use, and tumor characteristics. The pattern of genetic change in SCCHN can then be used to identify prognostically favorable and unfavorable groups for survival, disease- free survival, or disease recurrence. The information will be valuable in developing therapeutic interventions and experimental treatment protocols. From an unselected, prospectively ascertained series of about 240 SCCHN patients, the applicant will collect normal and tumor DNA, demographic data, history of past and current tobacco use, histopathological findings, and treatments. Patients will be followed for 2-5 years for disease-free survival, recurrence, and appearance of second primary tumors. Eight chromosomal regions will be tested for loss and instability at sites of microsatellite repeat polymorphism (MSRP), using polymerase chain reaction (PCR) assays. For each of the eight regions, three MSRP loci will be tested. MSRP loci were selected for their location within the region of interest, high level of heterozygosity in the normal population, and proximity to known or suspected tumor suppressor genes. DNA from peripheral blood from each patient will serve as the control. This information will be used to show the prognostic and biologic importance of specific genetic changes in SCCHN.
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| Rybicki, Benjamin A; Savera, Adnan T; Gomez, Jose A et al. (2003) Allelic loss and tumor pathology in head and neck squamous cell carcinoma. Mod Pathol 16:970-9 |
| Jones, J W; Raval, J R; Beals, T F et al. (1997) Frequent loss of heterozygosity on chromosome arm 18q in squamous cell carcinomas. Identification of 2 regions of loss--18q11.1-q12.3 and 18q21.1-q23. Arch Otolaryngol Head Neck Surg 123:610-4 |
