Transcriptomic landscape identifies two unrecognized ependymoma subtypes and novel pathways in medulloblastoma.

Autor:	Arora S; Human Biology Division, Fred Hutchinson Cancer Center, Seattle, WA, USA. 2., Nuechterlein N; Neuropathology Unit, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA., Jensen M; Human Biology Division, Fred Hutchinson Cancer Center, Seattle, WA, USA. 2., Glatzer G; Human Biology Division, Fred Hutchinson Cancer Center, Seattle, WA, USA. 2., Sievers P; Dept. of Neuropathology, University Hospital Heidelberg, and CCU Neuropathology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany., Varadharajan S; Developmental Neurobiology Department, Neurobiology and Brain Tumor Program, St Jude Children's Research Hospital, Memphis, TN, 38105., Korshunov A; Dept. of Neuropathology, University Hospital Heidelberg, and CCU Neuropathology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany., Sahm F; Dept. of Neuropathology, University Hospital Heidelberg, and CCU Neuropathology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany., Mack SC; Developmental Neurobiology Department, Neurobiology and Brain Tumor Program, St Jude Children's Research Hospital, Memphis, TN, 38105., Taylor MD; Neuro-oncology Research Program, Department of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine, Houston, Texas., Holland EC; Human Biology Division, Fred Hutchinson Cancer Center, Seattle, WA, USA. 2.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Oct 22. Date of Electronic Publication: 2024 Oct 22.
DOI:	10.1101/2024.10.21.619495
Abstrakt:	Medulloblastoma and ependymoma are prevalent pediatric central nervous system tumors with significant molecular and clinical heterogeneity. We collected bulk RNA sequencing data from 888 medulloblastoma and 370 ependymoma tumors to establish a comprehensive reference landscape. Following rigorous batch effect correction, normalization, and dimensionality reduction, we constructed a unified landscape to explore gene expression, signaling pathways, gene fusions, and copy number variations. Our analysis revealed distinct clustering patterns, including two primary ependymoma compartments, EPN-E1 and EPN-E2, each with specific gene fusions and molecular signatures. In medulloblastoma, we achieved precise stratification of Group 3/4 tumors by subtype and in SHH tumors by patient age. Our landscape serves as a vital resource for identifying biomarkers, refining diagnoses, and enables the mapping of new patients' bulk RNA-seq data onto the reference framework to facilitate accurate disease subtype identification. The landscape is accessible via Oncoscape, an interactive platform, empowering global exploration and application. Competing Interests: Competing interests Although the majority of Oncoscape has been open source for many years, a provisional patent has been filed on subset of the technology and computational algorithms presented in this paper, and N.N, S.A, M.J and E.C.H are listed as inventors (Serial No.: 63/595,717).
Databáze:	MEDLINE
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