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000127746 0247_ $$2doi$$a10.1007/s00401-015-1389-0
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000127746 0247_ $$2ISSN$$a1432-0533
000127746 037__ $$aDKFZ-2017-03769
000127746 041__ $$aeng
000127746 082__ $$a610
000127746 1001_ $$aWang, Xin$$b0
000127746 245__ $$aMedulloblastoma subgroups remain stable across primary and metastatic compartments.
000127746 260__ $$aBerlin$$bSpringer$$c2015
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000127746 520__ $$aMedulloblastoma comprises four distinct molecular variants with distinct genetics, transcriptomes, and outcomes. Subgroup affiliation has been previously shown to remain stable at the time of recurrence, which likely reflects their distinct cells of origin. However, a therapeutically relevant question that remains unanswered is subgroup stability in the metastatic compartment. We assembled a cohort of 12-paired primary-metastatic tumors collected in the MAGIC consortium, and established their molecular subgroup affiliation by performing integrative gene expression and DNA methylation analysis. Frozen tissues were collected and profiled using Affymetrix gene expression arrays and Illumina methylation arrays. Class prediction and hierarchical clustering were performed using existing published datasets. Our molecular analysis, using consensus integrative genomic data, establishes the unequivocal maintenance of molecular subgroup affiliation in metastatic medulloblastoma. We further validated these findings by interrogating a non-overlapping cohort of 19 pairs of primary-metastatic tumors from the Burdenko Neurosurgical Institute using an orthogonal technique of immunohistochemical staining. This investigation represents the largest reported primary-metastatic paired cohort profiled to date and provides a unique opportunity to evaluate subgroup-specific molecular aberrations within the metastatic compartment. Our findings further support the hypothesis that medulloblastoma subgroups arise from distinct cells of origin, which are carried forward from ontogeny to oncology.
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000127746 7001_ $$aDubuc, Adrian M$$b1
000127746 7001_ $$aRamaswamy, Vijay$$b2
000127746 7001_ $$aMack, Stephen$$b3
000127746 7001_ $$aGendoo, Deena M A$$b4
000127746 7001_ $$aRemke, Marc$$b5
000127746 7001_ $$aWu, Xiaochong$$b6
000127746 7001_ $$aGarzia, Livia$$b7
000127746 7001_ $$aLuu, Betty$$b8
000127746 7001_ $$aCavalli, Florence$$b9
000127746 7001_ $$aPeacock, John$$b10
000127746 7001_ $$aLópez, Borja$$b11
000127746 7001_ $$aSkowron, Patryk$$b12
000127746 7001_ $$aZagzag, David$$b13
000127746 7001_ $$aLyden, David$$b14
000127746 7001_ $$aHoffman, Caitlin$$b15
000127746 7001_ $$aCho, Yoon-Jae$$b16
000127746 7001_ $$aEberhart, Charles$$b17
000127746 7001_ $$aMacDonald, Tobey$$b18
000127746 7001_ $$aLi, Xiao-Nan$$b19
000127746 7001_ $$aVan Meter, Timothy$$b20
000127746 7001_ $$0P:(DE-HGF)0$$aNorthcott, Paul A$$b21
000127746 7001_ $$aHaibe-Kains, Benjamin$$b22
000127746 7001_ $$aHawkins, Cynthia$$b23
000127746 7001_ $$aRutka, James T$$b24
000127746 7001_ $$aBouffet, Eric$$b25
000127746 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan$$b26$$udkfz
000127746 7001_ $$0P:(DE-He78)8d9c904a6cea14d4c99c78ba46e41f93$$aKorshunov, Andrey$$b27$$udkfz
000127746 7001_ $$aTaylor, Michael D$$b28
000127746 773__ $$0PERI:(DE-600)1458410-4$$a10.1007/s00401-015-1389-0$$gVol. 129, no. 3, p. 449 - 457$$n3$$p449 - 457$$tActa neuropathologica$$v129$$x1432-0533$$y2015
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