TY  - JOUR
AU  - Wang, Xin
AU  - Dubuc, Adrian M
AU  - Ramaswamy, Vijay
AU  - Mack, Stephen
AU  - Gendoo, Deena M A
AU  - Remke, Marc
AU  - Wu, Xiaochong
AU  - Garzia, Livia
AU  - Luu, Betty
AU  - Cavalli, Florence
AU  - Peacock, John
AU  - López, Borja
AU  - Skowron, Patryk
AU  - Zagzag, David
AU  - Lyden, David
AU  - Hoffman, Caitlin
AU  - Cho, Yoon-Jae
AU  - Eberhart, Charles
AU  - MacDonald, Tobey
AU  - Li, Xiao-Nan
AU  - Van Meter, Timothy
AU  - Northcott, Paul A
AU  - Haibe-Kains, Benjamin
AU  - Hawkins, Cynthia
AU  - Rutka, James T
AU  - Bouffet, Eric
AU  - Pfister, Stefan
AU  - Korshunov, Andrey
AU  - Taylor, Michael D
TI  - Medulloblastoma subgroups remain stable across primary and metastatic compartments.
JO  - Acta neuropathologica
VL  - 129
IS  - 3
SN  - 1432-0533
CY  - Berlin
PB  - Springer
M1  - DKFZ-2017-03769
SP  - 449 - 457
PY  - 2015
AB  - Medulloblastoma 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:25689980
C2  - pmc:PMC4333718
DO  - DOI:10.1007/s00401-015-1389-0
UR  - https://inrepo02.dkfz.de/record/127746
ER  -