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000290890 1001_ $$0P:(DE-He78)34b3639de467b2c700920d7cbc3d2110$$aOkonechnikov, Konstantin$$b0$$eFirst author$$udkfz
000290890 245__ $$aClinically unfavorable transcriptome subtypes of non-WNT/non-SHH medulloblastomas are associated with a predominance in proliferating and progenitor-like cell subpopulations.
000290890 260__ $$aHeidelberg$$bSpringer$$c2024
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000290890 520__ $$aThe non-WNT/non-SHH (Grp3/Grp4) medulloblastomas (MBs) include eight second-generation subgroups (SGS; I-VIII) each with distinct molecular and clinical characteristics. Recently, we also identified two prognostically relevant transcriptome subtypes within each SGS MB, which are associated with unique gene expression signatures and signaling pathways. These prognostic subsets may be in connection to the intra-tumoral cell landscape that underlies SGS MB clinical-molecular diversity. Here, we performed a deconvolution analysis of the Grp3/Grp4 MB bulk RNA profiles using the previously identified single-cell RNA-seq reference dataset and focusing on variability in the cellular composition of SGS MB. RNA deconvolution analysis of the Grp3/Grp4 MB disclosed the subgroup-specific neoplastic cell subpopulations. Neuronally differentiated axodendritic GP3-C1 and glutamatergic GP4-C1 subpopulations were distributed within Grp3- and Grp4-associated SGS MB, respectively. Progenitor GP3-B2 subpopulation was prominent in aggressive SGS II MB, whereas photoreceptor/visual perception GP3/4-C2 cell content was typical for SGS III/IV MB. The current study also revealed significant variability in the proportions of cell subpopulations between clinically relevant SGS MB transcriptome subtypes, where unfavorable cohorts were enriched with cell cycle and progenitor-like cell subpopulations and, vice versa, favorable subtypes were composed of neuronally differentiated cell fractions predominantly. A higher than median proportion of proliferating and progenitor cell subpopulations conferred the shortest survival of the Grp3 and Grp 4 MB, and similar survival associations were identified for all SGS MB except SGS IV MB. In summary, the recently identified clinically relevant Grp3/Grp4 MB transcriptome subtypes are composed of different cell populations. Future studies should aim to validate the prognostic and therapeutic role of the identified Grp3/Grp4 MB inter-tumoral cellular heterogeneity. The application of the single-cell techniques on each SGS MB separately could help to clarify the clinical significance of subgroup-specific variability in tumor cell content and its relation with prognostic transcriptome signatures identified before.
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000290890 650_7 $$2Other$$aDeconvolution
000290890 650_7 $$2Other$$aMedulloblastoma
000290890 650_7 $$2Other$$aNon-WNT/non-SHH
000290890 650_7 $$2Other$$aPrognosis
000290890 650_7 $$2Other$$aSubgroups
000290890 650_2 $$2MeSH$$aHumans
000290890 650_2 $$2MeSH$$aMedulloblastoma: genetics
000290890 650_2 $$2MeSH$$aMedulloblastoma: pathology
000290890 650_2 $$2MeSH$$aMedulloblastoma: metabolism
000290890 650_2 $$2MeSH$$aTranscriptome
000290890 650_2 $$2MeSH$$aCerebellar Neoplasms: genetics
000290890 650_2 $$2MeSH$$aCerebellar Neoplasms: pathology
000290890 650_2 $$2MeSH$$aCerebellar Neoplasms: metabolism
000290890 650_2 $$2MeSH$$aCell Proliferation: genetics
000290890 650_2 $$2MeSH$$aMale
000290890 650_2 $$2MeSH$$aChild
000290890 650_2 $$2MeSH$$aFemale
000290890 650_2 $$2MeSH$$aChild, Preschool
000290890 650_2 $$2MeSH$$aAdolescent
000290890 650_2 $$2MeSH$$aPrognosis
000290890 7001_ $$0P:(DE-He78)e54a1e0999c1d8c95869ef9188b794cc$$aSchrimpf, Daniel$$b1$$udkfz
000290890 7001_ $$aKoster, Jan$$b2
000290890 7001_ $$0P:(DE-He78)8aad075b17d93a5636a34942bdbd7ee6$$aSievers, Philipp$$b3$$udkfz
000290890 7001_ $$0P:(DE-He78)0be2f86573954f87e97f8a4dbb05cb0f$$aMilde, Till$$b4$$udkfz
000290890 7001_ $$0P:(DE-He78)a1f4b408b9155beb2a8f7cba4d04fe88$$aSahm, Felix$$b5$$udkfz
000290890 7001_ $$0P:(DE-He78)551bb92841f634070997aa168d818492$$aJones, David T W$$b6$$udkfz
000290890 7001_ $$0P:(DE-He78)a8a10626a848d31e70cfd96a133cc144$$avon Deimling, Andreas$$b7$$udkfz
000290890 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan M$$b8$$udkfz
000290890 7001_ $$0P:(DE-He78)4c28e2aade5f44d8eca9dd8e97638ec8$$aKool, Marcel$$b9$$udkfz
000290890 7001_ $$0P:(DE-He78)8d9c904a6cea14d4c99c78ba46e41f93$$aKorshunov, Andrey$$b10$$eLast author$$udkfz
000290890 773__ $$0PERI:(DE-600)1458410-4$$a10.1007/s00401-024-02746-6$$gVol. 147, no. 1, p. 95$$n1$$p95$$tActa neuropathologica$$v147$$x0001-6322$$y2024
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