Journal Article DKFZ-2023-02178

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Tumor heterogeneity and tumor-microglia interactions in primary and recurrent IDH1-mutant gliomas.

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2023
Elsevier Maryland Heights, MO

Cell reports / Medicine 4(11), 101249 () [10.1016/j.xcrm.2023.101249]
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Abstract: The isocitrate dehydrogenase (IDH) gene is recurrently mutated in adult diffuse gliomas. IDH-mutant gliomas are categorized into oligodendrogliomas and astrocytomas, each with unique pathological features. Here, we use single-nucleus RNA and ATAC sequencing to compare the molecular heterogeneity of these glioma subtypes. In addition to astrocyte-like, oligodendrocyte progenitor-like, and cycling tumor subpopulations, a tumor population enriched for ribosomal genes and translation elongation factors is primarily present in oligodendrogliomas. Longitudinal analysis of astrocytomas indicates that the proportion of tumor subpopulations remains stable in recurrent tumors. Analysis of tumor-associated microglia/macrophages (TAMs) reveals significant differences between oligodendrogliomas, with astrocytomas harboring inflammatory TAMs expressing phosphorylated STAT1, as confirmed by immunohistochemistry. Furthermore, inferred receptor-ligand interactions between tumor subpopulations and TAMs may contribute to TAM state diversity. Overall, our study sheds light on distinct tumor populations, TAM heterogeneity, TAM-tumor interactions in IDH-mutant glioma subtypes, and the relative stability of tumor subpopulations in recurrent astrocytomas.

Keyword(s): IDH mutation ; astrocytoma ; bone-marrow-derived macrophages ; glioma ; microglia ; oligodendroglioma ; recurrent glioma ; snATAC-seq ; snRNA-seq ; tumor microenvironment

Classification:

Note: #EA:B062#LA:B320# / 2023 Nov 21;4(11):101249

Contributing Institute(s):
  1. B062 Pädiatrische Neuroonkologie (B062)
  2. DKTK HD zentral (HD01)
  3. Lichtmikroskopie (W210)
  4. KKE Neuroonkologie (B320)
  5. KKE Neuropathologie (B300)
Research Program(s):
  1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2023
Database coverage:
Medline ; DOAJ ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 10 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
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 Record created 2023-10-27, last modified 2024-02-29



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