Exploring Genome Reorganization and Gene Expression in Cancer Metastasis

Author

Saurav Kiri

Date of Award

2023

Document Type

Thesis

Degree Name

Bachelors

Department

Natural Sciences

First Advisor

Ryba, Tyrone

Area of Concentration

Cellular and Molecular Biology with Mathematics Secondary Field and Chemistry Secondary Field

Abstract

Cancer describes a broad group of diseases that results from ubiquitous and unchecked cellular growth and proliferation. Cancer is the second leading cause of death in the United States and disease burden is expected to increase globally throughout the next several decades, with the majority of cancer-related deaths occurring due to metastatic disease. Cancer cells exhibit known hallmarks that endow them with increased survival and proliferative capabilities, frequently as a result of de-stabilizing mutations. However, the genomic features that resolve metastatic clones from primary tumors are not yet well-characterized, as no mutational landscape has been identified as predictive of metastasis. This suggests a larger role for non-mutational genome re-organization in promoting dissemination. In this thesis, we analyzed sequencing datasets to interrogate epigenetic reprogramming as related to gene expression in metastases relative to primary tumors to discern pathways that may be indicative of metastasis. We additionally checked the pluripotency signature of metastases relative to primary tumors to determine whether disseminating clones attain a more embryonic stem cell-like state than their non-metastatic counterparts. We were unable to verify this hypothesis, but we confirmed consistent enrichment of cancer hallmarks across tumor systems and discovered possible future sources of investigation for selectively identifying cells with metastatic potential.

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