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Published on: November 2, 2020
An in vivo screen identifies ependymoma oncogenes and tumor-suppressor genes
Kumarasamypet M Mohankumar1, David S Currle1, Elsie White1
1Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Abstract:
Cancers are characterized by non-random chromosome copy number alterations that presumably contain oncogenes and tumor-suppressor genes (TSGs). The affected loci are often large, making it difficult to pinpoint which genes are driving the cancer. Here we report a cross-species in vivo screen of 84 candidate oncogenes and 39 candidate TSGs, located within 28 recurrent chromosomal alterations in ependymoma. Through a series of mouse models, we validate eight new ependymoma oncogenes and ten new ependymoma TSGs that converge on a small number of cell functions, including vesicle trafficking, DNA modification and cholesterol biosynthesis, identifying these as potential new therapeutic targets.
Insights
Researchers identified new oncogenes and tumor suppressor genes (TSGs) driving ependymoma cancer. This study pinpoints key cellular functions, offering potential new therapeutic targets for this brain tumor.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Cancers feature non-random chromosome copy number alterations harboring oncogenes and tumor suppressor genes (TSGs).
- Identifying specific driver genes within large affected chromosomal regions is challenging.
- Ependymoma is a type of brain tumor with recurrent chromosomal alterations.
Purpose of the Study:
- To identify novel oncogenes and TSGs involved in ependymoma development.
- To understand the cellular functions targeted by these genes.
- To discover potential new therapeutic strategies for ependymoma.
Main Methods:
- Conducted a cross-species in vivo screen of candidate oncogenes and TSGs.
- Focused on genes located within 28 recurrent chromosomal alterations in ependymoma.
- Utilized a series of mouse models for validation.
Main Results:
- Validated eight new ependymoma oncogenes.
- Validated ten new ependymoma tumor suppressor genes (TSGs).
- Identified convergence on key cellular functions: vesicle trafficking, DNA modification, and cholesterol biosynthesis.
Conclusions:
- Discovered novel genetic drivers of ependymoma.
- Highlighted the importance of vesicle trafficking, DNA modification, and cholesterol biosynthesis in ependymoma.
- These findings present potential new therapeutic targets for ependymoma treatment.
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