000148284 001__ 148284 000148284 005__ 20240229123030.0 000148284 0247_ $$2doi$$a10.1007/s00401-019-02102-z 000148284 0247_ $$2pmid$$apmid:31781912 000148284 0247_ $$2ISSN$$a0001-6322 000148284 0247_ $$2ISSN$$a1432-0533 000148284 0247_ $$2altmetric$$aaltmetric:71354401 000148284 037__ $$aDKFZ-2019-02850 000148284 041__ $$aeng 000148284 082__ $$a610 000148284 1001_ $$0P:(DE-He78)8d9c904a6cea14d4c99c78ba46e41f93$$aKorshunov, Andrey$$b0$$eFirst author$$udkfz 000148284 245__ $$aTranscriptional profiling of medulloblastoma with extensive nodularity (MBEN) reveals two clinically relevant tumor subsets with VSNL1 as potent prognostic marker. 000148284 260__ $$aHeidelberg$$bSpringer$$c2020 000148284 3367_ $$2DRIVER$$aarticle 000148284 3367_ $$2DataCite$$aOutput Types/Journal article 000148284 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1601365925_28271 000148284 3367_ $$2BibTeX$$aARTICLE 000148284 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000148284 3367_ $$00$$2EndNote$$aJournal Article 000148284 500__ $$a2020 Mar;139(3):583-596.#EA:B300#LA:B300# 000148284 520__ $$aMedulloblastoma with extensive nodularity (MBEN) is one of the few central nervous system (CNS) tumor entities occurring in infants which is traditionally associated with good to excellent prognosis. Some MBEN, however, have been reported with an unfavorable clinical course. We performed an integrated DNA/RNA-based molecular analysis of a multi-institutional MBEN cohort (n = 41) to identify molecular events which might be responsible for variability in patients' clinical outcomes. RNA sequencing analysis of this MBEN cohort disclosed two clear transcriptome clusters (TCL) of these CNS tumors: 'TCL1 MBEN' and 'TCL2 MBEN' which were associated with various gene expression signatures, mutational landscapes and, importantly, prognosis. Thus, the clinically unfavorable 'TCL1 MBEN' subset revealed transcriptome signatures composed of cancer-associated signaling pathways and disclosed a high frequency of clinically relevant germline PTCH1/SUFU alterations. In contrast, gene expression profiles of tumors from the clinically favorable 'TCL2 MBEN' subgroup were associated with activation of various neurometabolic and neurotransmission signaling pathways, and germline SHH-pathway gene mutations were extremely rare in this transcriptome cluster. 'TCL2 MBEN' also revealed strong and ubiquitous expression of VSNL1 (visinin-like protein 1) both at the mRNA and protein level, which was correlated with a favorable clinical course. Thus, combining mutational and epigenetic profiling with transcriptome analysis including VSNL1 immunohistochemistry, MBEN patients could be stratified into clinical risk groups of potential value for subsequent treatment planning. 000148284 536__ $$0G:(DE-HGF)POF3-312$$a312 - Functional and structural genomics (POF3-312)$$cPOF3-312$$fPOF III$$x0 000148284 588__ $$aDataset connected to CrossRef, PubMed, 000148284 7001_ $$0P:(DE-He78)34b3639de467b2c700920d7cbc3d2110$$aOkonechnikov, Konstantin$$b1$$udkfz 000148284 7001_ $$0P:(DE-He78)a1f4b408b9155beb2a8f7cba4d04fe88$$aSahm, Felix$$b2$$udkfz 000148284 7001_ $$aRyzhova, Marina$$b3 000148284 7001_ $$0P:(DE-He78)d20d08adc992abdb6ccffa1686f1ba17$$aStichel, Damian$$b4$$udkfz 000148284 7001_ $$0P:(DE-He78)e54a1e0999c1d8c95869ef9188b794cc$$aSchrimpf, Daniel$$b5$$udkfz 000148284 7001_ $$0P:(DE-HGF)0$$aGhasemi, David R$$b6 000148284 7001_ $$0P:(DE-He78)a7c1bbac024fa232d9c6b78443328d9d$$aPajtler, Kristian W$$b7$$udkfz 000148284 7001_ $$aAntonelli, Manila$$b8 000148284 7001_ $$aDonofrio, Vittoria$$b9 000148284 7001_ $$aMastronuzzi, Angela$$b10 000148284 7001_ $$aRossi, Sabrina$$b11 000148284 7001_ $$aCamassei, Francesca Diomedi$$b12 000148284 7001_ $$aBuccoliero, Anna Maria$$b13 000148284 7001_ $$aHaberler, Christine$$b14 000148284 7001_ $$aSlavc, Irene$$b15 000148284 7001_ $$aDahiya, Sonika$$b16 000148284 7001_ $$0P:(DE-He78)1e5010244cbd57412baa2f0e2806a182$$aCasalini, Belen$$b17$$udkfz 000148284 7001_ $$0P:(DE-He78)8aad075b17d93a5636a34942bdbd7ee6$$aSievers, Philipp$$b18$$udkfz 000148284 7001_ $$0P:(DE-He78)b6273c0ba3ae37a4d3d1c6b084797f2e$$aMeyer, Jochen$$b19$$udkfz 000148284 7001_ $$aKumirova, Ella$$b20 000148284 7001_ $$aZheludkova, Olga$$b21 000148284 7001_ $$aGolanov, Andrey$$b22 000148284 7001_ $$0P:(DE-He78)551bb92841f634070997aa168d818492$$aJones, David T W$$b23$$udkfz 000148284 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan M$$b24$$udkfz 000148284 7001_ 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