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| 041 | _ | _ | |a eng |
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| 100 | 1 | _ | |a Korshunov, Andrey |0 P:(DE-He78)8d9c904a6cea14d4c99c78ba46e41f93 |b 0 |e First author |
| 245 | _ | _ | |a Integrated molecular analysis of adult Sonic Hedgehog (SHH)-activated medulloblastomas reveals two clinically relevant tumor subsets with VEGFA as potent prognostic indicator. |
| 260 | _ | _ | |a Oxford |c 2021 |b Oxford Univ. Press |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1641314532_11028 |2 PUB:(DE-HGF) |
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| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 500 | _ | _ | |a #EA:B300#B062#LA:B062# / 2021 Sep 1;23(9):1576-1585 |
| 520 | _ | _ | |a Up to now, adult medulloblastoma (MB) patients are treated according to the protocols elaborated for pediatric MB although these tumors are different in terms of clinical outcomes and biology. Approximately 70% of adult MB disclose a Sonic Hedgehog (SHH) molecular signature in contrast to about 30% in pediatric cohorts. In addition, adult SHH-MB (aSHH-MB) are clinically heterogeneous but there is consensus neither on their optimal treatment nor on risk stratification. Thus, the identification of clinically relevant molecular subsets of aSHH-MB and identification of potential treatment targets remains inconclusive.We analyzed 96 samples of institutionally diagnosed aSHH-MB through genome-wide DNA methylation profiling, targeted DNA sequencing and RNA sequencing to identify molecular subcategories of these tumors and assess their prognostic significance.We defined two aSHH-MB numerically comparable epigenetic subsets with clinical and molecular variability. The subset 'aSHH-MBI' (46/48%) was associated with PTCH1/SMO (54%/46%) mutations, 'neuronal' transcriptional signatures, and favorable outcomes after combined radio-chemotherapy (5-year PFS = 80% and OS = 92%). The clinically unfavorable 'aSHH-MBII' subset (50/52%; 5-year PFS = 24% and OS = 45%) disclosed GLI2 amplifications (8%), loss of 10q (22%), and gene expression signatures associated with angiogenesis and embryonal development. aSHH-MBII tumors revealed strong and ubiquitous expression of VEGFA both at transcript and protein levels that was correlated with unfavorable outcome.1. The histologically uniform aSHH-MB cohort exhibits clear molecular heterogeneity separating these tumors into two molecular subsets (aSHH-MBI and aSHH-MBII), which are associated with different cytogenetics, mutational landscapes, gene expression signatures, and clinical course. 2. VEGFA appears to be a promising biomarker to predict clinical course, which needs further prospective validation as its potential role in the pathogenesis of this subset. |
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| 650 | _ | 7 | |a Adult |2 Other |
| 650 | _ | 7 | |a Medulloblastoma |2 Other |
| 650 | _ | 7 | |a SHH |2 Other |
| 650 | _ | 7 | |a VEGFA |2 Other |
| 650 | _ | 7 | |a prognosis |2 Other |
| 650 | _ | 7 | |a transcriptome |2 Other |
| 700 | 1 | _ | |a Okonechnikov, Konstantin |0 P:(DE-He78)34b3639de467b2c700920d7cbc3d2110 |b 1 |e First author |
| 700 | 1 | _ | |a Stichel, Damian |0 P:(DE-He78)d20d08adc992abdb6ccffa1686f1ba17 |b 2 |
| 700 | 1 | _ | |a Ryzhova, Marina |b 3 |
| 700 | 1 | _ | |a Schrimpf, Daniel |0 P:(DE-He78)e54a1e0999c1d8c95869ef9188b794cc |b 4 |
| 700 | 1 | _ | |a Sahm, Felix |0 P:(DE-He78)a1f4b408b9155beb2a8f7cba4d04fe88 |b 5 |
| 700 | 1 | _ | |a Sievers, Philipp |0 P:(DE-He78)8aad075b17d93a5636a34942bdbd7ee6 |b 6 |
| 700 | 1 | _ | |a Absalyamova, Oksana |b 7 |
| 700 | 1 | _ | |a Zheludkova, Olga |b 8 |
| 700 | 1 | _ | |a Golanov, Andrey |b 9 |
| 700 | 1 | _ | |a Jones, David T W |0 P:(DE-He78)551bb92841f634070997aa168d818492 |b 10 |
| 700 | 1 | _ | |a Pfister, Stefan M |0 P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9 |b 11 |
| 700 | 1 | _ | |a von Deimling, Andreas |0 P:(DE-He78)a8a10626a848d31e70cfd96a133cc144 |b 12 |
| 700 | 1 | _ | |a Kool, Marcel |0 P:(DE-He78)4c28e2aade5f44d8eca9dd8e97638ec8 |b 13 |e Last author |
| 773 | _ | _ | |a 10.1093/neuonc/noab031 |0 PERI:(DE-600)2094060-9 |n 9 |p 1576-1585 |t Neuro-Oncology |v 23 |y 2021 |x 1523-5866 |
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