TY  - JOUR
AU  - Shih, David J H
AU  - Northcott, Paul A
AU  - Remke, Marc
AU  - Korshunov, Andrey
AU  - Ramaswamy, Vijay
AU  - Kool, Marcel
AU  - Luu, Betty
AU  - Yao, Yuan
AU  - Wang, Xin
AU  - Dubuc, Adrian M
AU  - Garzia, Livia
AU  - Peacock, John
AU  - Mack, Stephen C
AU  - Wu, Xiaochong
AU  - Rolider, Adi
AU  - Morrissy, A Sorana
AU  - Cavalli, Florence M G
AU  - Jones, David
AU  - Zitterbart, Karel
AU  - Faria, Claudia C
AU  - Schüller, Ulrich
AU  - Kren, Leos
AU  - Kumabe, Toshihiro
AU  - Tominaga, Teiji
AU  - Shin Ra, Young
AU  - Garami, Miklós
AU  - Hauser, Peter
AU  - Chan, Jennifer A
AU  - Robinson, Shenandoah
AU  - Bognár, László
AU  - Klekner, Almos
AU  - Saad, Ali G
AU  - Liau, Linda M
AU  - Albrecht, Steffen
AU  - Fontebasso, Adam
AU  - Cinalli, Giuseppe
AU  - De Antonellis, Pasqualino
AU  - Zollo, Massimo
AU  - Cooper, Michael K
AU  - Thompson, Reid C
AU  - Bailey, Simon
AU  - Lindsey, Janet C
AU  - Di Rocco, Concezio
AU  - Massimi, Luca
AU  - Michiels, Erna M C
AU  - Scherer, Stephen W
AU  - Phillips, Joanna J
AU  - Gupta, Nalin
AU  - Fan, Xing
AU  - Muraszko, Karin M
AU  - Vibhakar, Rajeev
AU  - Eberhart, Charles G
AU  - Fouladi, Maryam
AU  - Lach, Boleslaw
AU  - Jung, Shin
AU  - Wechsler-Reya, Robert J
AU  - Fèvre-Montange, Michelle
AU  - Jouvet, Anne
AU  - Jabado, Nada
AU  - Pollack, Ian F
AU  - Weiss, William A
AU  - Lee, Ji-Yeoun
AU  - Cho, Byung-Kyu
AU  - Kim, Seung-Ki
AU  - Wang, Kyu-Chang
AU  - Leonard, Jeffrey R
AU  - Rubin, Joshua B
AU  - de Torres, Carmen
AU  - Lavarino, Cinzia
AU  - Mora, Jaume
AU  - Cho, Yoon-Jae
AU  - Tabori, Uri
AU  - Olson, James M
AU  - Gajjar, Amar
AU  - Packer, Roger J
AU  - Rutkowski, Stefan
AU  - Pomeroy, Scott L
AU  - French, Pim J
AU  - Kloosterhof, Nanne K
AU  - Kros, Johan M
AU  - Van Meir, Erwin G
AU  - Clifford, Steven C
AU  - Bourdeaut, Franck
AU  - Delattre, Olivier
AU  - Doz, François F
AU  - Hawkins, Cynthia E
AU  - Malkin, David
AU  - Grajkowska, Wieslawa A
AU  - Perek-Polnik, Marta
AU  - Bouffet, Eric
AU  - Rutka, James T
AU  - Pfister, Stefan
AU  - Taylor, Michael D
TI  - Cytogenetic prognostication within medulloblastoma subgroups.g
JO  - Journal of clinical oncology
VL  - 32
IS  - 9
SN  - 1527-7755
CY  - Alexandria, Va.
PB  - American Society of Clinical Oncology
M1  - DKFZ-2018-00257
SP  - 886 - 896
PY  - 2014
AB  - Medulloblastoma comprises four distinct molecular subgroups: WNT, SHH, Group 3, and Group 4. Current medulloblastoma protocols stratify patients based on clinical features: patient age, metastatic stage, extent of resection, and histologic variant. Stark prognostic and genetic differences among the four subgroups suggest that subgroup-specific molecular biomarkers could improve patient prognostication.Molecular biomarkers were identified from a discovery set of 673 medulloblastomas from 43 cities around the world. Combined risk stratification models were designed based on clinical and cytogenetic biomarkers identified by multivariable Cox proportional hazards analyses. Identified biomarkers were tested using fluorescent in situ hybridization (FISH) on a nonoverlapping medulloblastoma tissue microarray (n = 453), with subsequent validation of the risk stratification models.Subgroup information improves the predictive accuracy of a multivariable survival model compared with clinical biomarkers alone. Most previously published cytogenetic biomarkers are only prognostic within a single medulloblastoma subgroup. Profiling six FISH biomarkers (GLI2, MYC, chromosome 11 [chr11], chr14, 17p, and 17q) on formalin-fixed paraffin-embedded tissues, we can reliably and reproducibly identify very low-risk and very high-risk patients within SHH, Group 3, and Group 4 medulloblastomas.Combining subgroup and cytogenetic biomarkers with established clinical biomarkers substantially improves patient prognostication, even in the context of heterogeneous clinical therapies. The prognostic significance of most molecular biomarkers is restricted to a specific subgroup. We have identified a small panel of cytogenetic biomarkers that reliably identifies very high-risk and very low-risk groups of patients, making it an excellent tool for selecting patients for therapy intensification and therapy de-escalation in future clinical trials.
KW  - Biomarkers, Tumor (NLM Chemicals)
KW  - GLI2 protein, human (NLM Chemicals)
KW  - Hedgehog Proteins (NLM Chemicals)
KW  - Kruppel-Like Transcription Factors (NLM Chemicals)
KW  - MYC protein, human (NLM Chemicals)
KW  - Nuclear Proteins (NLM Chemicals)
KW  - Proto-Oncogene Proteins c-myc (NLM Chemicals)
KW  - SHH protein, human (NLM Chemicals)
KW  - Wnt Proteins (NLM Chemicals)
KW  - Zinc Finger Protein Gli2 (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:24493713
C2  - pmc:PMC3948094
DO  - DOI:10.1200/JCO.2013.50.9539
UR  - https://inrepo02.dkfz.de/record/132593
ER  -