Allelic imbalance at 11q in oral cancer and premalignant lesions

Oral squamous carcinomas (SCC) remain a significant public health problem worldwide despite advances in therapy and local disease control. New innovative strategies must be developed for the prevention, early detection and treatment of oral carcinoma. Such approaches will be heavily dependent on a better understanding of the molecular mechanisms underlying carcinogenesis at this site. This thesis describes a series of studies done on oral cancers and premalignant lesions to better define the role of alterations on chromosome 11 in the development of oral cancer at this site. Although numerous studies have reported the presence of alterations on this chromosome arm in oral cancers, few studies have examined premalignant lesions in order to determine whether such alterations play a role in the development of the disease. The objectives of this thesis were: 1) to use microsatellite analysis to examine DNA extracted from severe dysplasia, carcinoma in situ (CIS) and SCC for novel alterations on 11q;2) to determine at what stage of oral cancer development the alteration occurred by performing microsatellite analysis on a spectrum of stages of oral premalignant lesions (hyperplasia, mild dysplasia, moderate dysplasia, severe dysplasia, CIS) as well as invasive SCC. The data obtained was compared to 2 previously studied hotspots on 11q: the int2 (11q13) and D11S1778 (11q22-23); and 3) to determine the significance of allelic imbalance (Al) at int2 (11q13 ) and D11S1778 (11q22-23) to the progression of oral premalignant lesions by comparing frequencies of loss for different locus in low-grade dysplasia with known outcome, i.e. low-grade lesions that did not progress into cancer with morphologically similar lesions that did develop into SCC. In summary, the data suggest that at least 3 regions of alteration are present on 11q in both oral premalignant and malignant lesions and that 1 of these regions, identified as containing the novel marker D11S4207, might play a significant role in the early development of the disease. The data further support the use of these markers to identify progression risk for early oral premalignant lesions.Dentistry, Faculty ofGraduat