Adaptive Evolution in Cancer Metastasis
Abstract/Contents
- Abstract
- Metastasis is the spread of cancer from primary sites to distant regions of the body, called metastatic sites, and is responsible for nearly 90% of cancer deaths. Nevertheless, there exist few therapeutic options for the treatment of metastatic cancer. Thus, understanding of metastasis is critical to developing new clinical insights and therapeutic options. Cancer and metastasis are evolutionary processes driven at least in part by genetic changes that are generated under drift and selection. Somatic copy number alterations (SCNAs), the most common genetic change in the cancer genome, occur when multiple copies of the genome are gained or lost and have been shown to strongly influence cancer gene expression. While previous studies have predominantly focused on SCNAs and gene expression patterns in primary cancer, fewer studies have investigated their role in metastatic cancer. This study focused on SCNAs and identified gene expression patterns under selection during the process of metastasis, in which the corresponding genes were hypothesized to underlie metastasis. We developed a statistical approach based on the quantitative trait loci sign test, a well-established method to detect selection, to identify SCNAs and gene expression patterns under selection specifically in metastasis. We found 4,588 genes under selection more in metastatic cancer than primary cancer, including SMAD9, PLAC1, TTC28, TSTD3, and SMO. Importantly, we found that the genes under selection more in metastatic cancer than primary cancer were up-enriched for tolerance induction, a process that inhibits the immune system, and down-enriched for opsonization, a process that marks targets of the immune system. This suggests that the evasion of the immune system may be a critical process that allows metastasis to occur. In sum, this study identified candidate driver genes that underlie metastasis. Identifying such driver genes may contribute to the development of new clinical insights and therapeutic options, and ultimately reduce the massive contribution of metastasis to cancer morbidity and mortality.
Description
| Type of resource | text |
|---|---|
| Date created | June 2021 |
Creators/Contributors
| Author | Lee, Jiwoo |
|---|---|
| Primary advisor | Fraser, Hunter |
| Advisor | Winslow, Monte |
| Degree granting institution | Stanford University, Department of Biology, 2021 |
Subjects
| Subject | Biology |
|---|---|
| Subject | Cancer |
| Subject | Metastasis |
| Subject | Genetics |
| Subject | Evolution |
| Genre | Thesis |
Bibliographic information
Access conditions
- Use and reproduction
- User agrees that, where applicable, content will not be used to identify or to otherwise infringe the privacy or confidentiality rights of individuals. Content distributed via the Stanford Digital Repository may be subject to additional license and use restrictions applied by the depositor.
- License
- This work is licensed under a Creative Commons Attribution Share Alike 3.0 Unported license (CC BY-SA).
Preferred citation
- Preferred Citation
- Lee, Jiwoo; Fraser, Hunter; Winslow, Monte. (2021). Adaptive Evolution in Cancer Metastasis. Stanford Digital Repository. Available at: https://purl.stanford.edu/pg825yx9857
Collection
Undergraduate Theses, Department of Biology, 2020-2021
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- Contact
- jiwoolee@stanford.edu
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