Oral Presentations - Pathology and Laboratory Medicine - University ...

Graduate StudentAbstract # 41Shevaun E. HughesShevaun E. Hughes 1 , Ivy F.L. Tsui 1 , Catherine Poh 2,3 , and Cathie Garnis1,21Department of Cancer Genetics and Developmental Biology, British Columbia CancerResearch Centre, Vancouver, BC, Departments of 2 Surgery and 3 Oral Biological and MedicalSciences, University of British Columbia, Vancouver, BCderegulation of oncogene and tumor suppressorexpression by methylation in early stage oral cancerBackround/ObjectivesOral cancer is one of the world’s leading causes of cancer death, with late stage disease diagnoses and high ratesof recurrence accounting for poor survival rates. Like many solid tumors, oral cancer develops through a series ofhistopathological stages from hyperplasia to dysplasia, to carcinoma in situ (CIS), and finally to invasive disease.Understanding the initiating genomic alterations leading to gene dysregulation, and subsequent disease development,will lead to earlier and more directed treatment therapies. DNA methylation is a mechanism that can control geneexpression and is known to be altered in several cancer types. Aberrant methylation has also been observed inpremalignant lesions (such as p16 in oral dysplasia). Our goal is to identify genes that exhibit aberrant methylationand subsequent expression changes in the earliest stages of oral cancer progression, as early intervention allows for thegreatest possible impact on patient survival.MethodsWe have profiled multiple histologically different (hyperplasia, dysplasia, and CIS) biopsies from 5 oral cancerpatients. Gene expression and methylation status across the genome was determined using the Agilent 4x44K andIllumina Infinium platforms respectively. Using strict thresholds we compiled a list of candidate genes that exhibiteddecreased expression with a corresponding increase in methylation, and vice versa.ResultsAs expected we observed a greater number of genes with increased expression and decreased methylation, withthis trend holding true when we integrate the data from the two platforms. Despite the overall abundanceof global hypomethylation, we observed a 2 fold increase in both the hypomethylation/increased expressionand the hypermethylation/decreased expression from hyperplasia/dysplasia to dysplasia/CIS. Focusing on thehypermethylation/decreased expression candidates we have identified several candidate genes that exhibit this trendacross multiple samples.ConclusionWe have shown that there are a number of genes dysregulated in the early stages of oral carcinogenesis due to aberrantmethylation patterns, which may be important in driving progression. Elucidating these genes could result in diagnosticmarkers and targets for therapeutic intervention, resulting in improved patient care and overall survival.52 2 0 1 0 * P o s t e r P r e s e n t a t i o n s