Charles Swanton, Professor of Cancer Medicine at the University College London Cancer Institute, shared a post on X about a recent article he and his colleagues co-authored, adding:
“We are thrilled to share our latest research in Cancer Discovery!
Grateful to all collaborators in this work, work led by Paul Mischel and Ben Werner, and to Imran Noorani and Magnus Haughey for driving this work!
Special thanks: team eDyNAmic, UCL, The Francis Crick Institute , and CGC/CRUK.
Extrachromosomal DNA (ecDNA) is widely present in the most devastating cancers, including glioblastoma. Yet, how ecDNA evolves within tumours over time and space has remained a major open question.
In our new study in Cancer Discovery, we combined computational modeling with multi-region whole-genome sequencing samples from 94 treatment-naive glioblastomas to map the spatiotemporal dynamics of ecDNA.
Some of our key findings:
- Oncogene-specific patterns of ecDNA evolution emerge from random segregation and differing fitness advantages.
- For the first time, we show EGFR-ecDNA often accumulates before tumour formation and likely in ‘normal’ brain, reaching high abundance, and aggressively driving cancer growth.
- EGFR variants (like EGFRvIII-ecDNA) emerge from wild-type EGFR-ecDNA, occurring early and expanding extensively. This is often the ‘second-hit’, causing cancer expansion.
These results introduce new concepts like ecDNA clonality and heteroplasmy, which may reshape how we interpret tumor evolution.
By uncovering how ecDNA composition shapes distinct evolutionary trajectories in glioblastoma, we hope this work provides a foundation for refined models of tumor progression—and ultimately, new therapeutic strategies.”
Title: Extrachromosomal DNA–Driven Oncogene Spatial Heterogeneity and Evolution in Glioblastoma
Authors: Imran Noorani, Magnus Haughey, Jens Luebeck, Andrew Rowan, Eva Grönroos, Francesco Terenzi, Ivy Tsz-Lo Wong, Davide Pradella, Marta Lisi, Jeanette Kittel, Natasha Sharma, Chris Bailey, Clare E. Weeden, Donald M. Bell, Eric Joo, Vittorio Barbè, Matthew G. Jones, King L. Hung, Emma L. Nye, Mary Green, Lucy Meader, Emma J. Norton, Mark Fabian, Nnennaya Kanu, Mariam Jamal-Hanjani, Thomas Santarius, Andrea Ventura, James A.R. Nicoll, Delphine Boche, Howard Y. Chang, Vineet Bafna, Weini Huang, Paul S. Mischel, Charles Swanton, Benjamin Werner
Read the Full Article on Cancer Discovery
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