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Adult and Pediatric Medulloblastomas Are Genetically Distinct and Require Different Algorithms for Molecular Risk Stratification

KORSHUNOV, Andrey ; REMKE, Marc ; REIFENBERGER, Guido ; RUTKOWSKI, Stefan ; SCHEURLEN, Wolfram ; KULOZIK, Andreas E ; VON DEIMLING, Andreas ; LICHTER, Peter ; PFISTER, Stefan M ; WERFT, Wiebke ; BENNER, Axel ; RYZHOVA, Marina ; WITT, Hendrik ; STURM, Dominik ; WITTMANN, Andrea ; SCHÖTTLER, Anna ; FELSBERG, Jörg

Journal of clinical oncology, 2010-06, Vol.28 (18), p.3054-3060 [Periódico revisado por pares]

Alexandria, VA: American Society of Clinical Oncology

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Título:
Adult and Pediatric Medulloblastomas Are Genetically Distinct and Require Different Algorithms for Molecular Risk Stratification
Autor: KORSHUNOV, Andrey ; REMKE, Marc ; REIFENBERGER, Guido ; RUTKOWSKI, Stefan ; SCHEURLEN, Wolfram ; KULOZIK, Andreas E ; VON DEIMLING, Andreas ; LICHTER, Peter ; PFISTER, Stefan M ; WERFT, Wiebke ; BENNER, Axel ; RYZHOVA, Marina ; WITT, Hendrik ; STURM, Dominik ; WITTMANN, Andrea ; SCHÖTTLER, Anna ; FELSBERG, Jörg
Assuntos: Adolescent ; Adult ; Algorithms ; beta Catenin - genetics ; Biomarkers, Tumor - genetics ; Carcinoma, Large Cell - classification ; Carcinoma, Large Cell - genetics ; Carcinoma, Large Cell - metabolism ; Cerebellar Neoplasms - classification ; Cerebellar Neoplasms - genetics ; Cerebellar Neoplasms - metabolism ; Child ; Child, Preschool ; Chromosome Aberrations ; Chromosomes, Human, Pair 10 - genetics ; Chromosomes, Human, Pair 17 - genetics ; Chromosomes, Human, Pair 6 - genetics ; Comparative Genomic Hybridization ; Female ; Humans ; Immunoenzyme Techniques ; In Situ Hybridization, Fluorescence ; Infant ; Male ; Medulloblastoma - classification ; Medulloblastoma - genetics ; Medulloblastoma - metabolism ; Middle Aged ; N-Myc Proto-Oncogene Protein ; Nuclear Proteins - genetics ; Oligonucleotide Array Sequence Analysis ; Oncogene Proteins - genetics ; Prognosis ; Proto-Oncogene Proteins c-myc - genetics ; Risk Assessment ; Tissue Array Analysis ; Young Adult
É parte de: Journal of clinical oncology, 2010-06, Vol.28 (18), p.3054-3060
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Descrição: Medulloblastoma (MB) is the most common malignant brain tumor in children, whereas it rarely presents in adults. We aimed to identify genetic aberrations in 146 adult MBs to evaluate age-dependent differences in tumor biology and adapt age-specific risk stratification models. As a screening set, we studied a cohort of 34 adult MBs by using array-based comparative genomic hybridization comparing molecular results with clinical data. DNA copy number aberrations identified as possible prognostic markers were validated in an independent cohort of 112 adult patients with MB by fluorescent in situ hybridization analysis. Results were compared with the data obtained from 404 pediatric patients with MB. CDK6 amplification, 10q loss, and 17q gain are the most powerful prognostic markers in adult MB. Whereas MYC/MYCN oncogene amplifications had a high prognostic value in pediatric MB, these aberrations were rarely observed in adult tumors. Surprisingly, adult MBs with 6q deletion and nuclear beta-catenin activation did not share the excellent prognosis with their pediatric counterparts. Adult MB is distinct from pediatric MB in terms of genomic aberrations and their impact on clinical outcomes. Therefore, adult MBs require age-specific risk stratification models. We propose a molecular staging system involving three distinct risk groups based on DNA copy number status of 10q and 17q.
Editor: Alexandria, VA: American Society of Clinical Oncology
Idioma: Inglês;Russo

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Adult and Pediatric Medulloblastomas Are Genetically Distinct and Require Different Algorithms for Molecular Risk Stratification

Alexandria, VA: American Society of Clinical Oncology

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