Identification and Characterization of Different Metabolic Subtypes in Cancer

Date
2020-01-07
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Abstract
Cancer is a leading cause of death worldwide. Genomics based approaches represent a dominant approach in oncological research. However, multiple processes can modify genetic information and impact cancer’s phenotype in a non-coding manner such as epigenetic events, transcription of various splice variants, expression of non-coding RNA and miRNA, and post-translational modifications of proteins. Therefore, molecular events that are further downstream of the genome (perhaps reflected by the proteome or the metabolome) may better reflect the tumour phenotype. One feature of cancer is perturbed metabolism. Some of the aberrant metabolic pathways may enhance tumour viability and growth, and these perturbed pathways may be susceptible to pharmacologic inhibition. Thus, our overall goal is to categorize tumours by their metabolic features; to understand the biological implications of these metabolic features, and to identify pathways that could be potentially targeted with drugs. This project involves the development of a workflow to define the metabolic features of a tumour. The workflow will involve the categorization of tumours based on their metabolic features (at the transcriptome level), exploration of associated biological features of each metabolic subtype, and integration of multiple levels of molecular control (including mutation status, copy number variation, methylation, and metabolome). Our work began with breast cancer, which is already well characterized by a large cohort in The Cancer Genome Atlas (TCGA) project. Then we used the same principles to investigate a more complex tumour type, pancreatic cancer, which is characterized by a highly variable degree of stroma infiltration.
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Keywords
Metabolism, Breast Cancer, Pancreatic Ductal Adenocarcinoma, Analytical Workflow, Deconvolution
Citation
Pervin, J. (2020). Identification and Characterization of Different Metabolic Subtypes in Cancer (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.