Distinct cellular functional profiles in pan-cancer expression analysis of cancers with alterations in oncogenes c-MYC and n-MYC

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    Linked Agent
    Creator (cre): Richardson, Anne B.
    Advisor (adv): Vernon, Dan
    May 9, 2018
    Graduation Year

    Cancerous cells may contain a vast array of dysregulated or altered genes that contribute to tumorigenesis, but there are often a few prominent oncogenic drivers that are very commonly found in a variety of cancers. The MYC gene family, composed of c-MYC, n-MYC, and l-MYC, is a group of basic helix-loop-helix leucine-zipper (bHLHZ) transcription factors that regulate expression of 15% of the human genome. MYC oncogenes drive the transcription of a variety of genes involved in the cell cycle, apoptosis, and cell growth. When constitutively expressed, they have been implicated in the genesis and progression of a variety of cancer types by contributing to unchecked cell proliferation. However, little research has been done on systemic, pan-cancer patterns and effects that MYC oncogenes may have on tumorigenesis. Using data from the Cancer Genome Atlas, I analyzed upregulated gene sets across 33 different tumor types associated with increased activity of c-MYC or its paralog n-MYC, in order to find pan-cancer patterns of gene expression and better understand the mechanisms of MYC-driven cancer. I confirmed the presence of a "canonical" functional profile previously documented in the literature, consisting of upregulated biological processes such as DNA replication and repair, RNA transcription, RNA processing, chromatin regulation, and protein translation. However, I also found a novel "non-canonical" functional profile correlated with a diverse set of cell signaling pathways, immune system function, and the extracellular matrix, which may be involved in the maintenance of a tumor microenvironment. These findings may be important for identifying potential therapeutic drug targets, as well as further elucidating the causes and mechanisms of MYC-driven cancer.

    55 pages
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