Genotype-specific chromatin accessibility states in cancer
Abstract/Contents
- Abstract
- Cancer is most often classified as a genetic disease, with cells accumulating mutations over time that allow for uncontrollable proliferation. However, mutations alone cannot account for all of the phenotypes that cancers exhibit. For example, metastatic cells have distinct morphologies, characteristics, and migratory abilities compared to their primary tumor counterparts, despite having nearly identical genotypes. To understand why this might happen, we must look beyond the genotype of cancer cells and instead focus on their epigenetic landscape, which involves how the genome is folded within the cell and which parts are readily accessible for transcription. This work first investigates how a mutation in the gene liver kinase B1 (LKB1) in lung cancer has the potential to enable metastasis, even though most cells with an identical mutation will never metastasize. Instead, it appears that a specific epigenetic switch must occur in order to initiate the metastatic cascade. In addition, this work describes a high-throughput method to profile the chromatin landscape of cancer cells after introducing engineered mutations or perturbations. This method minimizes the time and effort required to investigate the epigenetic consequences of additional genetic mutations in cancer, beyond just LKB1. Following decades of research into the origins of metastasis and the interplay between genetics and epigenetics, these studies highlight the importance of chromatin context in understanding the genetic underpinnings of cancer. These results have implications for predicting which patients are at highest risk for metastatic progression, understanding molecular subtypes of cancer as they relate to clinical stages, and identifying stage-specific vulnerabilities in cancer.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2021; ©2021 |
| Publication date | 2021; 2021 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Pierce, Sarah Elisabeth |
|---|---|
| Degree supervisor | Greenleaf, William James |
| Degree supervisor | Winslow, Monte |
| Thesis advisor | Greenleaf, William James |
| Thesis advisor | Winslow, Monte |
| Thesis advisor | Bassik, Michael |
| Thesis advisor | Khavari, Paul A |
| Degree committee member | Bassik, Michael |
| Degree committee member | Khavari, Paul A |
| Associated with | Stanford University, Cancer Biology Program |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Sarah Elisabeth Pierce. |
|---|---|
| Note | Submitted to the Cancer Biology Program. |
| Thesis | Thesis Ph.D. Stanford University 2021. |
| Location | https://purl.stanford.edu/tc268vz1402 |
Access conditions
- Copyright
- © 2021 by Sarah Elisabeth Pierce
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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