Genomic and transcriptional signatures of Epstein-Barr virus-associated malignancies
Abstract/Contents
- Abstract
- Epstein-Barr Virus (EBV) is causally associated with the development of malignancies across multiple tissue types. In transplant recipients, EBV can cause an aggressive spectrum of malignancies called post-transplant lymphoproliferative disorder (PTLD). Traditionally, it is thought that immunosuppression is the precipitating factor in the development of PTLD; however, only a small portion of transplant recipients develop PTLD. Here, we describe how EBV genome diversity, immune response, and cellular pathways contribute to development of EBV-associated malignancies, including PTLD. In chapter 2, we discuss how PTLD-associated variations potentially alter the immune response. We sequenced the EBV genome from transplant recipients with and without PTLD to determine which variations are unique to PTLD patients. We identified 15 novel PTLD-associated non-synonymous variations, including eight in EBNA3C. Then, we used NetMHC and NetMHCII to predict how these PTLD-associated variations alter the binding of EBV-derived peptides to HLA-A, -B, and -DR molecules. In chapter 3, we address the cellular pathways involved in EBV-oncogenesis. We conducted an integrative, multi- cohort meta-analysis of three gene expression datasets from PTLD, gastric cancer, and Hodgkin's lymphoma containing EBV-positive (EBV+) and EBV-negative (EBV-) tumor samples. We identified an EBV+ tumor gene signature that represents a network of genes that are commonly expressed in EBV infected cells across various cancers. Using siRNA and RNA-seq, we determined that one of the genes in the EBV+ tumor gene signature, C21orf91, regulates the expression of genes involved in NF-kB and Type I interferon signaling. Future directions of this work are summarized in chapter 4.
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 | 2019; ©2019 |
| Publication date | 2019; 2019 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Maloney, Eden Marie |
|---|---|
| Degree supervisor | Martinez, Olivia |
| Thesis advisor | Martinez, Olivia |
| Thesis advisor | Bhatt, Ami (Ami Siddharth) |
| Thesis advisor | Davis, Mark M |
| Thesis advisor | Khatri, Purvesh |
| Degree committee member | Bhatt, Ami (Ami Siddharth) |
| Degree committee member | Davis, Mark M |
| Degree committee member | Khatri, Purvesh |
| Associated with | Stanford University, Immunology Program. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Eden Marie Maloney. |
|---|---|
| Note | Submitted to the Immunology Program. |
| Thesis | Thesis Ph.D. Stanford University 2019. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2019 by Eden Marie Maloney
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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