title: Clinical and molecular stratification of disease risk in medulloblastoma.
abstract: The accurate assessment of disease risk among children with medulloblastoma remains a major challenge to the field of paediatric neuro-oncology. In the current study we investigated the capacity of molecular abnormalities to increase the accuracy of disease risk stratification above that afforded by clinical staging alone. 41 primary medulloblastoma tumour samples were analysed for ErbB2 receptor expression using immunohistochemistry, and for aberrations of chromosome 17 and amplification of the MYC oncogene using fluorescence in situ hybridisation. The ErbB2 receptor and deletion of 17p were detected in 80% and 49% of tumours, respectively. 17p loss occurred either in isolation (20%), or in association with gain of 17q (29%), compatible with an isochromosome of 17q. Amplification of MYC was detected in only 2 tumours. Significant prognostic factors included, 'metastatic disease' (P = 0.0006), 'sub-total tumour resection' (P = 0.007), 'high ErbB2 receptor expression' (P = 0.003) and 'isolated 17p loss' (P = 0.003). Combined analysis of clinical and molecular factors enabled greater resolution of disease risk than clinical factors alone, identifying a sub-population of patients with particularly favourable disease outcome. These data support the hypothesis that a combination of clinical and molecular factors may afford a more reliable means of assigning disease risk in patients with medulloblastoma, thereby providing a more accurate basis for targeting therapy in children with this disease.
authors.affiliation: Dept. Developmental Neurobiology, St Jude Children's Research Hospital, Room 2006G, 332 North Lauderdale St, Memphis, TN 38105, USA.
authors.forename: R
authors.initials: R
authors.lastname: Gilbertson
authors.forename: C
authors.initials: C
authors.lastname: Wickramasinghe
authors.forename: R
authors.initials: R
authors.lastname: Hernan
authors.forename: V
authors.initials: V
authors.lastname: Balaji
authors.forename: D
authors.initials: D
authors.lastname: Hunt
authors.forename: D
authors.initials: D
authors.lastname: Jones-Wallace
authors.forename: J
authors.initials: J
authors.lastname: Crolla
authors.forename: R
authors.initials: R
authors.lastname: Perry
authors.forename: J
authors.initials: J
authors.lastname: Lunec
authors.forename: A
authors.initials: A
authors.lastname: Pearson
authors.forename: D
authors.initials: D
authors.lastname: Ellison
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D002528:Cerebellar Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008527:Medulloblastoma / Q000235:genetics* / Q000378:metabolism / Q000556:secondary / Q000601:surgery; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D018570:Risk Assessment; D016019:Survival Analysis
chemical_list: D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases