Transcriptional dysregulation in diffuse intrinsic pontine glioma
Abstract/Contents
- Abstract
- Diffuse intrinsic pontine glioma (DIPG) is a fatal pediatric cancer with limited therapeutic options. The majority of cases of DIPG exhibit a mutation in histone-3 (H3K27M) that results in oncogenic transcriptional aberrancies. In this work, we study the mechanisms by which the H3K27M mutation reprograms the epigenome of DIPG, identifying core dysregulations driving its malignant state and novel strategies for treating this cancer. We show that DIPG is vulnerable to transcriptional disruption using bromodomain inhibition or CDK7 blockade and these targets may help overcome resistance to other forms of therapy. We additionally demonstrate that H3K27M chromatin remodeling and the resultant oncogenic state depend upon both the variant of histone-3 and the cell-context in which the mutation occurs. These studies allow for identification and validation of both shared and subgroup-specific pathophysiology of DIPG tumors, advancing the possibility of personalized therapy for this disease. Altogether, the work here provides a detailed characterization of the molecular profile of DIPG and identifies previously unknown pathophysiology important for future therapeutic development
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 | 2020; ©2020 |
| Publication date | 2020; 2020 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Nagaraja, Surya |
|---|---|
| Degree supervisor | Monje-Deisseroth, Michelle |
| Thesis advisor | Monje-Deisseroth, Michelle |
| Thesis advisor | Chang, Howard Y. (Howard Yuan-Hao), 1972- |
| Thesis advisor | Wysocka, Joanna, Ph. D |
| Degree committee member | Chang, Howard Y. (Howard Yuan-Hao), 1972- |
| Degree committee member | Wysocka, Joanna, Ph. D |
| Associated with | Stanford University, Department of Stem Cell Biology and Regenertaive Medicine Interdisciplinary. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Surya Nagaraja |
|---|---|
| Note | Submitted to the Department of Stem Cell Biology and Regenerative Medicine Interdisciplinary |
| Thesis | Thesis Ph.D. Stanford University 2020 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2020 by Surya Nagaraja
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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