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000170386 1001_ $$aColtin, Hallie$$b0
000170386 245__ $$aSubgroup and subtype-specific outcomes in adult medulloblastoma.
000170386 260__ $$aHeidelberg$$bSpringer$$c2021
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000170386 500__ $$a#LA:B300# / 2021 Nov;142(5):859-871
000170386 520__ $$aMedulloblastoma, a common pediatric malignant central nervous system tumour, represent a small proportion of brain tumours in adults. Previously it has been shown that in adults, Sonic Hedgehog (SHH)-activated tumours predominate, with Wingless-type (WNT) and Group 4 being less common, but molecular risk stratification remains a challenge. We performed an integrated analysis consisting of genome-wide methylation profiling, copy number profiling, somatic nucleotide variants and correlation of clinical variables across a cohort of 191 adult medulloblastoma cases identified through the Medulloblastoma Advanced Genomics International Consortium. We identified 30 WNT, 112 SHH, 6 Group 3, and 41 Group 4 tumours. Patients with SHH tumours were significantly older at diagnosis compared to other subgroups (p < 0.0001). Five-year progression-free survival (PFS) for WNT, SHH, Group 3, and Group 4 tumours was 64.4 (48.0-86.5), 61.9% (51.6-74.2), 80.0% (95% CI 51.6-100.0), and 44.9% (95% CI 28.6-70.7), respectively (p = 0.06). None of the clinical variables (age, sex, metastatic status, extent of resection, chemotherapy, radiotherapy) were associated with subgroup-specific PFS. Survival among patients with SHH tumours was significantly worse for cases with chromosome 3p loss (HR 2.9, 95% CI 1.1-7.6; p = 0.02), chromosome 10q loss (HR 4.6, 95% CI 2.3-9.4; p < 0.0001), chromosome 17p loss (HR 2.3, 95% CI 1.1-4.8; p = 0.02), and PTCH1 mutations (HR 2.6, 95% CI 1.1-6.2; p = 0.04). The prognostic significance of 3p loss and 10q loss persisted in multivariable regression models. For Group 4 tumours, chromosome 8 loss was strongly associated with improved survival, which was validated in a non-overlapping cohort (combined cohort HR 0.2, 95% CI 0.1-0.7; p = 0.007). Unlike in pediatric medulloblastoma, whole chromosome 11 loss in Group 4 and chromosome 14q loss in SHH was not associated with improved survival, where MYCN, GLI2 and MYC amplification were rare. In sum, we report unique subgroup-specific cytogenetic features of adult medulloblastoma, which are distinct from those in younger patients, and correlate with survival disparities. Our findings suggest that clinical trials that incorporate new strategies tailored to high-risk adult medulloblastoma patients are urgently needed.
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000170386 650_7 $$2Other$$aAdult
000170386 650_7 $$2Other$$aDNA methylation profiling
000170386 650_7 $$2Other$$aMedulloblastoma
000170386 650_7 $$2Other$$aMolecular groups
000170386 650_7 $$2Other$$aRisk stratification
000170386 7001_ $$aSundaresan, Lakshmikirupa$$b1
000170386 7001_ $$aSmith, Kyle S$$b2
000170386 7001_ $$aSkowron, Patryk$$b3
000170386 7001_ $$aMassimi, Luca$$b4
000170386 7001_ $$aEberhart, Charles G$$b5
000170386 7001_ $$aSchreck, Karisa C$$b6
000170386 7001_ $$aGupta, Nalin$$b7
000170386 7001_ $$aWeiss, William A$$b8
000170386 7001_ $$aTirapelli, Daniela$$b9
000170386 7001_ $$aCarlotti, Carlos$$b10
000170386 7001_ $$aLi, Kay K W$$b11
000170386 7001_ $$aRyzhova, Marina$$b12
000170386 7001_ $$aGolanov, Andrey$$b13
000170386 7001_ $$aZheludkova, Olga$$b14
000170386 7001_ $$aAbsalyamova, Oksana$$b15
000170386 7001_ $$0P:(DE-He78)34b3639de467b2c700920d7cbc3d2110$$aOkonechnikov, Konstantin$$b16$$udkfz
000170386 7001_ $$0P:(DE-He78)d20d08adc992abdb6ccffa1686f1ba17$$aStichel, Damian$$b17$$udkfz
000170386 7001_ $$0P:(DE-He78)a8a10626a848d31e70cfd96a133cc144$$avon Deimling, Andreas$$b18$$udkfz
000170386 7001_ $$aGiannini, Caterina$$b19
000170386 7001_ $$aRaskin, Scott$$b20
000170386 7001_ $$aVan Meir, Erwin G$$b21
000170386 7001_ $$aChan, Jennifer A$$b22
000170386 7001_ $$aFults, Daniel$$b23
000170386 7001_ $$aChambless, Lola B$$b24
000170386 7001_ $$aKim, Seung-Ki$$b25
000170386 7001_ $$aVasiljevic, Alexandre$$b26
000170386 7001_ $$aFaure-Conter, Cecile$$b27
000170386 7001_ $$aVibhakar, Rajeev$$b28
000170386 7001_ $$aJung, Shin$$b29
000170386 7001_ $$aLeary, Sarah$$b30
000170386 7001_ $$aMora, Jaume$$b31
000170386 7001_ $$aMcLendon, Roger E$$b32
000170386 7001_ $$aPollack, Ian F$$b33
000170386 7001_ $$aHauser, Peter$$b34
000170386 7001_ $$aGrajkowska, Wieslawa A$$b35
000170386 7001_ $$aRubin, Joshua B$$b36
000170386 7001_ $$avan Veelen, Marie-Lise C$$b37
000170386 7001_ $$aFrench, Pim J$$b38
000170386 7001_ $$aKros, Johan M$$b39
000170386 7001_ $$aLiau, Linda M$$b40
000170386 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan M$$b41$$udkfz
000170386 7001_ $$0P:(DE-He78)4c28e2aade5f44d8eca9dd8e97638ec8$$aKool, Marcel$$b42$$udkfz
000170386 7001_ $$aKijima, Noriyuki$$b43
000170386 7001_ $$aTaylor, Michael D$$b44
000170386 7001_ $$aPacker, Roger J$$b45
000170386 7001_ $$aNorthcott, Paul A$$b46
000170386 7001_ $$0P:(DE-He78)8d9c904a6cea14d4c99c78ba46e41f93$$aKorshunov, Andrey$$b47$$eLast author$$udkfz
000170386 7001_ $$00000-0002-6557-895X$$aRamaswamy, Vijay$$b48
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