Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

An estimated 4% to 7% of the population will develop a clinically significant thyroid tumor during their lifetime. In many cases, diagnosis results from standard techniques are inconclusive and so a large proportion of individuals undergo surgery as a diagnostic procedure for cancer. The suspicious mass, however, is found to be malignant in only 20% of all cases. Several studies have evaluated malignant and benign thyroid lesions in order to identify molecular markers that allow for accurate diagnosis; none have proved sensitive and specific enough for clinical use. The underlying mechanisms that cause thyroid malignant and benign tumors are still poorly understood and hence the need for a more comprehensive analysis. The emergence of the massively parallel "next-generation" sequencing technologies has made possible the thorough examination of tumors on the level of DNA and as a result the identification of most of the mutations in tumor samples. Several individuals' genomes and tumor samples have been sequenced for a small fraction of the cost of sequencing the first human genome. We have undertaken a complete sequence analysis of thyroid cancers in order to characterize, for the first time, the underlying molecular mechanism of this disease. Utilizing these technologies, we have sequenced the genetic material of dissected tumors in addition to normal tissues, such as blood, from the same patients. This will allow us to identify the novel mutations that have given rise to the disease in each individual patient. Systematic comparison between the tumors allows commonly mutated genes in thyroid cancers to be identified. Such analysis will help in determining the molecular changes causing the disease, identifying more sensitive diagnostics as well as the proteins and pathways important for therapeutic interventions.