title: Prognostic classification of pediatric medulloblastoma based on chromosome 17p loss, expression of MYCC and MYCN, and Wnt pathway activation.
abstract: Pediatric medulloblastoma is considered a highly heterogeneous disease and a new strategy of risk stratification to optimize therapeutic outcomes is required. We aimed to investigate a new risk-stratification approach based on expression profiles of medulloblastoma cohorts. We analyzed gene expression profiles of 30 primary medulloblastomas and detected strong evidence that poor survival outcome was significantly associated with mRNA expression profiles of 17p loss. However, it was not supported in independent cohorts from previously published data (n = 100). We speculated that this discrepancy might come from complex conditions of two important prognostic determinants: loss of tumor suppressors (chromosome 17p) and high expression of oncogenes c-myc (MYCC) or N-myc (MYCN). When patients were stratified into 5 or 7 subgroups based on simultaneous consideration of these 2 factors while defining the Wnt group as independent, obviously different survival expectancies were detected between the subgroups. For instance, predicted 5-year survival probabilities ranged from 19% to 81% in the 5 subgroups. We also found that age became a significant prognostic marker after adjusting for 17p, MYCC, and MYCN status. Diminished survival in age <3 years was more substantial in subgroups with high expression of MYCC, MYCN, or 17p loss but not in other subgroups, indicating that poor survival outcome might be synergistically affected by these 3 factors. Here we suggest a more tailored subgrouping system based on expression profiles of chromosome 17p, MYCC, and MYCN, which could provide the basis for a novel risk-stratification strategy in pediatric medulloblastoma.
authors.affiliation: College of Pharmacy, Sunchon National University, Korea.
authors.forename: Ae Kyung
authors.initials: AK
authors.lastname: Park
authors.forename: Seung-Jun
authors.initials: SJ
authors.lastname: Lee
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Phi
authors.forename: Kyu-Chang
authors.initials: KC
authors.lastname: Wang
authors.forename: Dong Gyu
authors.initials: DG
authors.lastname: Kim
authors.forename: Byung-Kyu
authors.initials: BK
authors.lastname: Cho
authors.forename: Christine
authors.initials: C
authors.lastname: Haberler
authors.forename: Sarah
authors.initials: S
authors.lastname: Fattet
authors.forename: Christelle
authors.initials: C
authors.lastname: Dufour
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Puget
authors.forename: Christian
authors.initials: C
authors.lastname: Sainte-Rose
authors.forename: Franck
authors.initials: F
authors.lastname: Bourdeaut
authors.forename: Jacques
authors.initials: J
authors.lastname: Grill
authors.forename: Olivier
authors.initials: O
authors.lastname: Delattre
authors.forename: Seung-Ki
authors.initials: SK
authors.lastname: Kim
authors.forename: Woong-Yang
authors.initials: WY
authors.lastname: Park
mesh_terms: D014408:Biomarkers, Tumor; D002528:Cerebellar Neoplasms / Q000145:classification / Q000235:genetics / Q000401:mortality*; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D016259:Genes, myc; D006801:Humans; D007223:Infant; D008297:Male; D008527:Medulloblastoma / Q000145:classification / Q000235:genetics / Q000401:mortality*; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D058496:Smith-Magenis Syndrome; D016019:Survival Analysis; D060449:Wnt Signaling Pathway / Q000502:physiology*
chemical_list: D014408:Biomarkers, Tumor; C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc
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