PMID- 19255330
OWN - NLM
STAT- MEDLINE
DCOM- 20090429
LR  - 20161125
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Linking)
VI  - 27
IP  - 10
DP  - 2009 Apr 1
TI  - Outcome prediction in pediatric medulloblastoma based on DNA copy-number 
      aberrations of chromosomes 6q and 17q and the MYC and MYCN loci.
PG  - 1627-36
LID - 10.1200/JCO.2008.17.9432 [doi]
AB  - PURPOSE: Medulloblastoma is the most common malignant brain tumor in children. 
      Current treatment decisions are based on clinical variables. Novel tumor-derived 
      biomarkers may improve the risk stratification of medulloblastoma patients. 
      PATIENTS AND METHODS: A model for the molecular risk stratification was proposed 
      from an array-based comparative genomic hybridization (array-CGH) screen (n = 
      80). Fluorescence in situ hybridization (FISH) analyses for chromosome arms 6q, 
      17p, and 17q and the MYC and MYCN loci were performed in an independent 
      validation set (n = 260). Copy number aberrations were correlated with clinical, 
      histologic, and survival data. RESULTS: Gain of 6q and 17q and genomic 
      amplification of MYC or MYCN were each associated with poor outcome in the 
      array-CGH study (n = 80). In contrast, all patients with 6q-deleted tumors 
      survived. Given these findings, the following hierarchical molecular staging 
      system was defined: (1) MYC/MYCN amplification, (2) 6q gain, (3) 17q gain, (4) 6q 
      and 17q balanced, and (5) 6q deletion. The prognostic value of this staging 
      system was investigated by FISH analysis (n = 260). The addition of molecular 
      markers to clinical risk factors resulted in the identification of a large 
      proportion of patients (72 of 260 patients; 30%) at high risk for relapse and 
      death who would be considered standard risk by application of clinical variables 
      alone. CONCLUSION: Genomic aberrations in medulloblastoma are powerful 
      independent markers of disease progression and survival. By adding genomic 
      markers to established clinical and histologic variables, outcome prediction can 
      be substantially improved. Because the analyses can be conducted on routine 
      paraffin-embedded material, it will be especially feasible to use this novel 
      molecular staging system in large multicenter clinical trials.
FAU - Pfister, Stefan
AU  - Pfister S
AD  - Division of Molecular Genetics and Biostatistics and Clinical Cooperation Unit 
      Neuropathology, German Cancer Research Center, Department of Pediatric Oncology, 
      Hematology and Immunology, University of Heidelberg, Heidelberg, Germany. 
      s.pfister@dkfz.de
FAU - Remke, Marc
AU  - Remke M
FAU - Benner, Axel
AU  - Benner A
FAU - Mendrzyk, Frank
AU  - Mendrzyk F
FAU - Toedt, Grischa
AU  - Toedt G
FAU - Felsberg, Jorg
AU  - Felsberg J
FAU - Wittmann, Andrea
AU  - Wittmann A
FAU - Devens, Frauke
AU  - Devens F
FAU - Gerber, Nicolas U
AU  - Gerber NU
FAU - Joos, Stefan
AU  - Joos S
FAU - Kulozik, Andreas
AU  - Kulozik A
FAU - Reifenberger, Guido
AU  - Reifenberger G
FAU - Rutkowski, Stefan
AU  - Rutkowski S
FAU - Wiestler, Otmar D
AU  - Wiestler OD
FAU - Radlwimmer, Bernhard
AU  - Radlwimmer B
FAU - Scheurlen, Wolfram
AU  - Scheurlen W
FAU - Lichter, Peter
AU  - Lichter P
FAU - Korshunov, Andrey
AU  - Korshunov A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090302
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (MYCN protein, human)
RN  - 0 (N-Myc Proto-Oncogene Protein)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Oncogene Proteins)
SB  - IM
MH  - Area Under Curve
MH  - Cerebellar Neoplasms/*genetics/mortality
MH  - Child
MH  - Child, Preschool
MH  - Chromosome Aberrations
MH  - Chromosomes, Human, Pair 17/*genetics
MH  - Chromosomes, Human, Pair 6/*genetics
MH  - Comparative Genomic Hybridization
MH  - Female
MH  - Gene Dosage
MH  - Genes, myc/*genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - Medulloblastoma/*genetics/mortality
MH  - N-Myc Proto-Oncogene Protein
MH  - Nuclear Proteins/*genetics
MH  - Oncogene Proteins/*genetics
MH  - Prognosis
MH  - ROC Curve
MH  - Tissue Array Analysis
EDAT- 2009/03/04 09:00
MHDA- 2009/04/30 09:00
CRDT- 2009/03/04 09:00
PHST- 2009/03/04 09:00 [entrez]
PHST- 2009/03/04 09:00 [pubmed]
PHST- 2009/04/30 09:00 [medline]
AID - JCO.2008.17.9432 [pii]
AID - 10.1200/JCO.2008.17.9432 [doi]
PST - ppublish
SO  - J Clin Oncol. 2009 Apr 1;27(10):1627-36. doi: 10.1200/JCO.2008.17.9432. Epub 2009 
      Mar 2.