ArticleActa neuropathologica communications2022
Convergent evolution and multi-wave clonal invasion in H3 K27-altered diffuse midline gliomas treated with a PDGFR inhibitor.
Article in Acta neuropathologica communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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7 citing papers in PubMed, 8 citations in OpenAlex.
- Cell autonomous regional differences in oligodendrocyte lineage development and responses to oncohistone H3.3 K27M.Nature communications · 2026Article
- Molecular features unique to circulating tumor DNA enable the tumor-naïve liquid biopsy of glioblastoma.NPJ precision oncology · 2026Article
- Seq2Karyotype (S2K): A Method forbioRxiv : the preprint server for biology · 2025Article
- The oncolytic adenovirus Delta-24-RGD in combination with ONC201 induces a potent antitumor response in pediatric high-grade and diffuse midline glioma models.Neuro-oncology · 2024Article
- Subclonal Cancer Driver Mutations Are Prevalent in the Unresected Peritumoral Edema of Adult Diffuse Gliomas.Cancer research · 2024Article
- Oncohistones and disrupted development in pediatric-type diffuse high-grade glioma.Cancer metastasis reviews · 2023Review
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16 authors at 3 institutions in 1 country.
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Abstract
The majority of diffuse midline gliomas, H3 K27-altered (DMG-H3 K27-a), are infiltrating pediatric brain tumors that arise in the pons with no effective treatment. To understand how clonal evolution contributes to the tumor's invasive spread, we performed exome sequencing and SNP array profiling on 49 multi-region autopsy samples from 11 patients with pontine DMG-H3 K27-a enrolled in a phase I clinical trial of PDGFR inhibitor crenolanib. For each patient, a phylogenetic tree was constructed by testing multiple possible clonal evolution models to select the one consistent with somatic mutations and copy number variations across all tumor regions. The tree was then used to deconvolute subclonal composition and prevalence at each tumor region to study convergent evolution and invasion patterns. Somatic variants in the PI3K pathway, a late event, are enriched in our cohort, affecting 70% of patients. Convergent evolution of PI3K at distinct phylogenetic branches was detected in 40% of the patients. 24 (~ 50%) of tumor regions were occupied by subclones of mixed lineages with varying molecular ages, indicating multiple waves of invasion across the pons and extrapontine. Subclones harboring a PDGFRA amplicon, including one that amplified a PDGRFA
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