New research from @jingyiwu.bsky.social, @drbradb.bsky.social, @suvalab.bsky.social, and others shows how slow-growing brain tumors called gliomas turn aggressive and deadly. The team pinpointed genetic shifts that push these tumors into the fast lane. #Science
Many thanks to the Damon Runyon Fellowship and Charles A. King Trust Fellowship, which funded my postdoc and supported this work & our supportive institutions @DFCI_Cancer Biology and @broadinstitute.org
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7/ Great team efforts with L. Nicolas Gonzalez Castro,
Sofia Battaglia, Chadi Elfarran, Joshua P. D’Antonio,
@tymillerlab.bsky.social, @suvalab.bsky.social, @drbradb.bsky.social
6/We speculated this model—where epigenetic events drive early clonal expansion and immune evasion, allowing tumors to progress until they acquire genetic mutations—may apply broadly across human cancers.
5/It also explains the distinct clinical behaviors of low- and high-grade IDH-mutant gliomas, including why low-grade tumors respond to IDH inhibitors, while high-grade ones do not.
4/This suggests that IDH mutations and hypermethylation suppress interferon (IFN) responses, which are crucial for the survival of these gliomas.
3/We also found these tumors initially depend on an epigenetic driver, DNA methylation, but later shift to genetic drivers, such as the deletion of tumor suppressors and interferon pathway genes.
2/ This suggests that IDH-mutant gliomas may begin with transforming OPCs into malignant OPC-like cells, followed by reprogramming into a highly proliferative NPC-like state.
1/We found that low-grade tumors primarily comprise cells resembling slow-proliferating oligodendrocyte precursor cells (OPCs), while high-grade tumors are dominated by cells resembling fast-proliferating neural progenitor cells (NPCs).
Our work reveals that as IDH mutant gliomas progress, their cell states and key drivers change. www.nature.com/articles/s43...
Thank you so much!
I am a cancer researcher at DFCI. Can I be added here? Thanks!
