Prognostic classification of pediatric medulloblastoma based on chromosome 17p loss, expression of MYCC and MYCN, and Wnt pathway activation
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 expressi...
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Published in | Neuro-oncology (Charlottesville, Va.) Vol. 14; no. 2; pp. 203 - 214 |
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Main Authors | , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
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Oxford University Press
01.02.2012
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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. |
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AbstractList | 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. 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. |
Author | Lee, Seung-Jun Sainte-Rose, Christian Wang, Kyu-Chang Park, Ae Kyung Kim, Dong Gyu Dufour, Christelle Park, Woong-Yang Fattet, Sarah Phi, Ji Hoon Puget, Stéphanie Kim, Seung-Ki Haberler, Christine Delattre, Olivier Bourdeaut, Franck Cho, Byung-Kyu Grill, Jacques |
AuthorAffiliation | College of Pharmacy, Sunchon National University , Korea (A.K.P.); Department of Neurosurgery , Inje University, Ilsan Paik Hospital , Gyeonggido , Korea (S.-J.L.); Departments of Neurosurgery (J.H.P., K.-C.W., D.G.K., B.-K.C., S.-K.K.) and Biomedical Sciences (W.-Y.P.) , Seoul National University College of Medicine , Seoul , Korea ; Institute of Neurology, Medical University of Vienna , Vienna , Austria , (C.H.); Service d'oncologiepédiatrique, Département médico-chirurgical de pédiatrie, Le Centre hospitalier universitaire vaudois, Lausanne, Suisse , (S.F.); Department of Pediatric and Adolescent Oncology , Gustave Roussy Cancer Institute , Villejuif, Paris, France (C.D., J.G.); Service de Neurochirurgie Pédiatrique , Hôpital Necker–Enfants Malades , (S.P., C.S.-R.); Institut Curie, Laboratoire de Genetique et Biologie des Cancers , Paris , France (F.B., O.D.) |
AuthorAffiliation_xml | – name: College of Pharmacy, Sunchon National University , Korea (A.K.P.); Department of Neurosurgery , Inje University, Ilsan Paik Hospital , Gyeonggido , Korea (S.-J.L.); Departments of Neurosurgery (J.H.P., K.-C.W., D.G.K., B.-K.C., S.-K.K.) and Biomedical Sciences (W.-Y.P.) , Seoul National University College of Medicine , Seoul , Korea ; Institute of Neurology, Medical University of Vienna , Vienna , Austria , (C.H.); Service d'oncologiepédiatrique, Département médico-chirurgical de pédiatrie, Le Centre hospitalier universitaire vaudois, Lausanne, Suisse , (S.F.); Department of Pediatric and Adolescent Oncology , Gustave Roussy Cancer Institute , Villejuif, Paris, France (C.D., J.G.); Service de Neurochirurgie Pédiatrique , Hôpital Necker–Enfants Malades , (S.P., C.S.-R.); Institut Curie, Laboratoire de Genetique et Biologie des Cancers , Paris , France (F.B., O.D.) |
Author_xml | – sequence: 1 givenname: Ae Kyung surname: Park fullname: Park, Ae Kyung organization: College of Pharmacy, Sunchon National University, Korea – sequence: 2 givenname: Seung-Jun surname: Lee fullname: Lee, Seung-Jun – sequence: 3 givenname: Ji Hoon surname: Phi fullname: Phi, Ji Hoon – sequence: 4 givenname: Kyu-Chang surname: Wang fullname: Wang, Kyu-Chang – sequence: 5 givenname: Dong Gyu surname: Kim fullname: Kim, Dong Gyu – sequence: 6 givenname: Byung-Kyu surname: Cho fullname: Cho, Byung-Kyu – sequence: 7 givenname: Christine surname: Haberler fullname: Haberler, Christine – sequence: 8 givenname: Sarah surname: Fattet fullname: Fattet, Sarah – sequence: 9 givenname: Christelle surname: Dufour fullname: Dufour, Christelle – sequence: 10 givenname: Stéphanie surname: Puget fullname: Puget, Stéphanie – sequence: 11 givenname: Christian surname: Sainte-Rose fullname: Sainte-Rose, Christian – sequence: 12 givenname: Franck surname: Bourdeaut fullname: Bourdeaut, Franck – sequence: 13 givenname: Jacques surname: Grill fullname: Grill, Jacques – sequence: 14 givenname: Olivier surname: Delattre fullname: Delattre, Olivier – sequence: 15 givenname: Seung-Ki surname: Kim fullname: Kim, Seung-Ki – sequence: 16 givenname: Woong-Yang surname: Park fullname: Park, Woong-Yang |
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Snippet | Pediatric medulloblastoma is considered a highly heterogeneous disease and a new strategy of risk stratification to optimize therapeutic outcomes is required.... |
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SubjectTerms | Biomarkers, Tumor Cerebellar Neoplasms - classification Cerebellar Neoplasms - genetics Cerebellar Neoplasms - mortality Child Child, Preschool Chromosome Deletion Chromosomes, Human, Pair 17 - genetics Chromosomes, Human, Pair 17 - metabolism Clinical Investigations Female Gene Expression Profiling Genes, myc Humans Infant Male Medulloblastoma - classification Medulloblastoma - genetics Medulloblastoma - mortality N-Myc Proto-Oncogene Protein Nuclear Proteins - genetics Nuclear Proteins - metabolism Oncogene Proteins - genetics Oncogene Proteins - metabolism Prognosis Proto-Oncogene Proteins c-myc - genetics Proto-Oncogene Proteins c-myc - metabolism Signal Transduction - physiology Smith-Magenis Syndrome Survival Analysis Wnt Signaling Pathway - physiology |
Title | Prognostic classification of pediatric medulloblastoma based on chromosome 17p loss, expression of MYCC and MYCN, and Wnt pathway activation |
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