Genetic and epigenetic features of cell-free DNA for the early detection of lung cancer
Abstract/Contents
- Abstract
- Lung cancer remains the leading cause of cancer deaths, due largely to the late stage at diagnosis for most patients. Patients diagnosed earlier and with smaller tumors have higher rates of survival, but current screening paradigms have low uptake. Here, we aim to develop blood-based assays to increase the number of people screened for lung cancer. To do this, we focus on cell-free DNA (cfDNA), or the short fragments of DNA found in the plasma compartment of the blood, which in patients with cancer can contain DNA shed directly from the malignant tumor cells. This circulating tumor DNA, or ctDNA, features tumor-specific mutations and epigenetic alterations, making it a promising biomarker for cancer. First, we aim to leverage genetic features of cfDNA to discriminate lung cancer samples from healthy ones, and develop a Lung Cancer Likelihood in Plasma (Lung-CLiP) model which can robustly discriminate early-stage lung cancer patients from risk-matched controls. Next, we aim to develop a novel method that harnesses epigenetic features of cfDNA for early lung cancer detection. We focus on DNA methylation, which is broadly dysregulated in cancer. We identify hundreds of loci at which methylation states distinguish non-small cell lung cancer (NSCLC) from healthy blood and lung samples, and using these regions we identify features of cfDNA methylation that distinguish patients from controls. A LASSO logistic regression model trained on these features shows stage-dependent sensitivity, suggesting biological plausibility, and outperforms a leading commercial method for Stage I tumors. Integration of genetic and epigenetic features may achieve optimal performance, and we aim to test that strategy in the near future.
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 | 2022; ©2022 |
| Publication date | 2022; 2022 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Hamilton, Emily Grace |
|---|---|
| Degree supervisor | Alizadeh, Ash |
| Degree supervisor | Diehn, Maximilian |
| Thesis advisor | Alizadeh, Ash |
| Thesis advisor | Diehn, Maximilian |
| Thesis advisor | Pollack, Jonathan D |
| Thesis advisor | Salzman, Julia |
| Thesis advisor | Sherlock, Gavin |
| Degree committee member | Pollack, Jonathan D |
| Degree committee member | Salzman, Julia |
| Degree committee member | Sherlock, Gavin |
| Associated with | Stanford University, Cancer Biology Program |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Emily G. Hamilton. |
|---|---|
| Note | Submitted to the Cancer Biology Program. |
| Thesis | Thesis Ph.D. Stanford University 2022. |
| Location | https://purl.stanford.edu/zx693kc6784 |
Access conditions
- Copyright
- © 2022 by Emily Grace Hamilton
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
Also listed in
Loading usage metrics...