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@ARTICLE{Shih:132593,
author = {D. J. H. Shih and P. A. Northcott$^*$ and M. Remke and A.
Korshunov$^*$ and V. Ramaswamy and M. Kool$^*$ and B. Luu
and Y. Yao and X. Wang and A. M. Dubuc and L. Garzia and J.
Peacock and S. C. Mack and X. Wu and A. Rolider and A. S.
Morrissy and F. M. G. Cavalli and D. Jones$^*$ and K.
Zitterbart and C. C. Faria and U. Schüller and L. Kren and
T. Kumabe and T. Tominaga and Y. Shin Ra and M. Garami and
P. Hauser and J. A. Chan and S. Robinson and L. Bognár and
A. Klekner and A. G. Saad and L. M. Liau and S. Albrecht and
A. Fontebasso and G. Cinalli and P. De Antonellis and M.
Zollo and M. K. Cooper and R. C. Thompson and S. Bailey and
J. C. Lindsey and C. Di Rocco and L. Massimi and E. M. C.
Michiels and S. W. Scherer and J. J. Phillips and N. Gupta
and X. Fan and K. M. Muraszko and R. Vibhakar and C. G.
Eberhart and M. Fouladi and B. Lach and S. Jung and R. J.
Wechsler-Reya and M. Fèvre-Montange and A. Jouvet and N.
Jabado and I. F. Pollack and W. A. Weiss and J.-Y. Lee and
B.-K. Cho and S.-K. Kim and K.-C. Wang and J. R. Leonard and
J. B. Rubin and C. de Torres and C. Lavarino and J. Mora and
Y.-J. Cho and U. Tabori and J. M. Olson and A. Gajjar and R.
J. Packer and S. Rutkowski and S. L. Pomeroy and P. J.
French and N. K. Kloosterhof and J. M. Kros and E. G. Van
Meir and S. C. Clifford and F. Bourdeaut and O. Delattre and
F. F. Doz and C. E. Hawkins and D. Malkin and W. A.
Grajkowska and M. Perek-Polnik and E. Bouffet and J. T.
Rutka and S. Pfister$^*$ and M. D. Taylor},
title = {{C}ytogenetic prognostication within medulloblastoma
subgroups.g},
journal = {Journal of clinical oncology},
volume = {32},
number = {9},
issn = {1527-7755},
address = {Alexandria, Va.},
publisher = {American Society of Clinical Oncology},
reportid = {DKFZ-2018-00257},
pages = {886 - 896},
year = {2014},
abstract = {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.},
keywords = {Biomarkers, Tumor (NLM Chemicals) / GLI2 protein, human
(NLM Chemicals) / Hedgehog Proteins (NLM Chemicals) /
Kruppel-Like Transcription Factors (NLM Chemicals) / MYC
protein, human (NLM Chemicals) / Nuclear Proteins (NLM
Chemicals) / Proto-Oncogene Proteins c-myc (NLM Chemicals) /
SHH protein, human (NLM Chemicals) / Wnt Proteins (NLM
Chemicals) / Zinc Finger Protein Gli2 (NLM Chemicals)},
cin = {G380 / B062},
ddc = {050},
cid = {I:(DE-He78)G380-20160331 / I:(DE-He78)B062-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:24493713},
pmc = {pmc:PMC3948094},
doi = {10.1200/JCO.2013.50.9539},
url = {https://inrepo02.dkfz.de/record/132593},
}