OS05.2.A DECIPHERING THE LONGITUDINAL TRAJECTORIES OF GLIOBLASTOMA ECOSYSTEMS BY INTEGRATIVE SINGLE-CELL GENOMICS Article Swipe
Alan R. Spitzer
,
Kevin C. Johnson
,
Masashi Nomura
,
Luciano Garofano
,
Djamel Nehar-Belaid
,
Noam Galili Darnell
,
Anthony G. Greenwald
,
Lillian Bussema
,
Yeonyee Oh
,
Frederick S. Varn
,
Francesca D’Angelo
,
S Gritsch
,
Kevin Anderson
,
S Migliozzi
,
L Gonzalez Castro
,
Tamrin Chowdhury
,
Nicolas Robine
,
Catherine Reeves
,
Jongsun Park
,
A Lipsa
,
Frank Hertel
,
Anna Golebiewska
,
Simone P. Niclou
,
Labeeba Nusrat
,
Salomey Kellett
,
Sunit Das
,
Hyeong‐Gon Moon
,
S Paek
,
Franck Bielle
,
Alice Laurenge
,
Anna Luisa Di Stefano
,
Bertrand Mathon
,
Alberto Pïcca
,
Marc Sanson
,
Shigenori Tanaka
,
Nobuhito Saito
,
David M. Ashley
,
Stephen T. Keir
,
Keith L. Ligon
,
J. T. Huse
,
W.K. Alfred Yung
,
Anna Lasorella
,
Antonio Iavarone
,
Roel G.W. Verhaak
,
Itay Tirosh
,
Mario L. Suvà
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1093/neuonc/noaf193.050
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1093/neuonc/noaf193.050
BACKGROUND The mechanisms governing the progression of IDH-wildtype glioblastoma (GBM) following standard-of-care therapy remain incompletely understood. While recurrence is nearly universal, the cellular and molecular trajectories that underpin this process - particularly the dynamics of tumor and microenvironmental compartments - have yet to be fully resolved. MATERIAL AND METHODS To dissect the longitudinal evolution of the GBM ecosystem, we analyzed paired primary and recurrent tumor specimens from 59 patients. We employed single-nucleus RNA sequencing to profile transcriptomic states at single-cell resolution and integrated these data with bulk DNA sequencing to assess genomic alterations. This approach enabled a comprehensive interrogation of cellular heterogeneity and malignant state transitions over time. RESULTS Across the cohort, the most consistent feature at recurrence was a decreased proportion of malignant cells, accompanied by a reciprocal expansion of non-malignant glial and neuronal cell populations within the tumor microenvironment (TME). While the dominant malignant cell state often differed between primary and recurrent samples, no state was uniquely associated with a specific disease stage. Moreover, no singular evolutionary trajectory characterized the cohort as a whole. Instead, subsets of patients exhibited enriched and partially convergent state transitions. Notably, shifts in malignant cell states were mirrored by concurrent remodeling of the TME, implicating a tightly interwoven pattern of tumor-microenvironment co-evolution. CONCLUSION These findings reveal diverse and patient-specific evolutionary trajectories in IDH-wildtype GBM, shaped by both therapeutic pressure and microenvironmental context. Our study provides a reference framework for understanding longitudinal GBM dynamics and highlights the importance of ecosystem-level interactions in driving recurrence.
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- article
- Language
- en
- Landing Page
- https://doi.org/10.1093/neuonc/noaf193.050
- https://academic.oup.com/neuro-oncology/article-pdf/27/Supplement_3/iii17/64483609/noaf193.050.pdf
- OA Status
- bronze
- OpenAlex ID
- https://openalex.org/W4414792320
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https://openalex.org/W4414792320Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1093/neuonc/noaf193.050Digital Object Identifier
- Title
-
OS05.2.A DECIPHERING THE LONGITUDINAL TRAJECTORIES OF GLIOBLASTOMA ECOSYSTEMS BY INTEGRATIVE SINGLE-CELL GENOMICSWork title
- Type
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articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2025Year of publication
- Publication date
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2025-10-01Full publication date if available
- Authors
-
Alan R. Spitzer, Kevin C. Johnson, Masashi Nomura, Luciano Garofano, Djamel Nehar-Belaid, Noam Galili Darnell, Anthony G. Greenwald, Lillian Bussema, Yeonyee Oh, Frederick S. Varn, Francesca D’Angelo, S Gritsch, Kevin Anderson, S Migliozzi, L Gonzalez Castro, Tamrin Chowdhury, Nicolas Robine, Catherine Reeves, Jongsun Park, A Lipsa, Frank Hertel, Anna Golebiewska, Simone P. Niclou, Labeeba Nusrat, Salomey Kellett, Sunit Das, Hyeong‐Gon Moon, S Paek, Franck Bielle, Alice Laurenge, Anna Luisa Di Stefano, Bertrand Mathon, Alberto Pïcca, Marc Sanson, Shigenori Tanaka, Nobuhito Saito, David M. Ashley, Stephen T. Keir, Keith L. Ligon, J. T. Huse, W.K. Alfred Yung, Anna Lasorella, Antonio Iavarone, Roel G.W. Verhaak, Itay Tirosh, Mario L. SuvàList of authors in order
- Landing page
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https://doi.org/10.1093/neuonc/noaf193.050Publisher landing page
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https://academic.oup.com/neuro-oncology/article-pdf/27/Supplement_3/iii17/64483609/noaf193.050.pdfDirect link to full text PDF
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https://academic.oup.com/neuro-oncology/article-pdf/27/Supplement_3/iii17/64483609/noaf193.050.pdfDirect OA link when available
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| primary_location.raw_source_name | Neuro-Oncology |
| primary_location.landing_page_url | https://doi.org/10.1093/neuonc/noaf193.050 |
| publication_date | 2025-10-01 |
| publication_year | 2025 |
| referenced_works_count | 0 |
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