Cross-species genomics matches driver mutations and cell compartments to model ependymoma
- Robert A Johnson 1, Karen D Wright , Helen Poppleton , Kumarasamypet M Mohankumar , David Finkelstein , Stanley B Pounds , Vikki Rand , Sarah E S Leary , Elsie White , Christopher Eden , Twala Hogg , Paul Northcott , Stephen Mack , Geoffrey Neale , Yong-Dong Wang , Beth Coyle , Jennifer Atkinson , Mariko DeWire , Tanya A Kranenburg , Yancey Gillespie , Jeffrey C Allen , Thomas Merchant , Fredrick A Boop , Robert A Sanford , Amar Gajjar , David W Ellison , Michael D Taylor , Richard G Grundy , Richard J Gilbertson
- 1Department of Developmental Neurobiology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA.
- 0Department of Developmental Neurobiology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA.
Related Experiment Videos
Contact us if these videos are not relevant.
Contact us if these videos are not relevant.
View abstract on PubMed
Summary
This summary is machine-generated.Researchers modeled brain tumors called ependymomas by matching genetic changes to specific neural stem cells. This approach accurately recreated a human tumor subgroup, revealing disrupted synaptogenesis as a key event in its development.
Area Of Science
- Neuro-oncology
- Cancer Genomics
- Developmental Neuroscience
Background
- Ependymomas exhibit histological similarity but molecular heterogeneity, complicating biological understanding.
- Identifying cancer's cellular origins and drivers is crucial for deciphering tumor subgroups.
Purpose Of The Study
- To decipher ependymoma heterogeneity by integrating genetic alterations with candidate cells of origin.
- To generate accurate ependymoma disease models using cross-species genomics.
Main Methods
- Subgrouping human ependymomas based on genetic alterations.
- Matching human tumor transcriptomes to mouse neural stem cells (NSCs) from various developmental stages and CNS regions.
- Utilizing Ink4a/Arf locus status in NSCs for cellular compartment selection.
- Activating Ephb2 signaling in matched NSCs to generate a mouse model.
Main Results
- Identified novel subgroup-specific genetic alterations in ependymoma.
- Matched human supratentorial ependymomas to embryonic cerebral Ink4a/Arf(-/-) NSCs based on transcriptomic profiles.
- Generated a highly penetrant mouse model of ependymoma by activating Ephb2 signaling in specific NSCs.
- Revealed deregulation of synaptogenesis genes in matched human and mouse tumors.
Conclusions
- Cross-species genomics effectively matches driver mutations with cellular origins for accurate cancer modeling.
- Disruption of synaptogenesis is a critical event in a specific subgroup of supratentorial ependymomas.
- This study provides a powerful framework for modeling and interrogating cancer subgroups.
Related Experiment Videos
Contact us if these videos are not relevant.
Contact us if these videos are not relevant.