• Neuro-oncology · Feb 2012

    Prognostic classification of pediatric medulloblastoma based on chromosome 17p loss, expression of MYCC and MYCN, and Wnt pathway activation.

    • Ae Kyung Park, Seung-Jun Lee, Ji Hoon Phi, Kyu-Chang Wang, Dong Gyu Kim, Byung-Kyu Cho, Christine Haberler, Sarah Fattet, Christelle Dufour, Stéphanie Puget, Christian Sainte-Rose, Franck Bourdeaut, Jacques Grill, Olivier Delattre, Seung-Ki Kim, and Woong-Yang Park.
    • College of Pharmacy, Sunchon National University, Korea.
    • Neuro-oncology. 2012 Feb 1; 14 (2): 203-14.

    AbstractPediatric 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.

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