title: Chromosome 9q and 16q loss identified by genome-wide pooled-analysis are associated with tumor aggressiveness in patients with classic medulloblastoma.
abstract: Medulloblastoma (MB) is one of the most aggressive pediatric brain tumor. We report genome-wide pooled-analysis of classic MB variant of patients over 3 years of age at diagnosis. We combined array comparative genomic hybridization (aCGH) results from experimental analysis (31 cases) with two public databases (55 cases) in a final evaluation of 86 MBs. The most common chromosome structural aberrations were gains of 17q (45.3%), 1q (22.1%), and losses of 8p (15.1%), 10q (19.8%), 17p (37.2%), and 16q (16.3%). Isochromome (17q) was observed in 29.1% MBs. A significant association between poor patients survival and losses of 9q (p < 0.0023), 10q (p < 0.012), and 16q (p < 0.036) was observed. Univariate analysis showed association of 9q loss (p < 0.008) and 16q loss (p = 0.05) with adverse overall survival (OS). Chromosome 6 monosomy was a protective event although statistically borderline (p = 0.066). After adjusting for confounding factors, a poor OS was found for patients whose tumor has 9q loss [hazard ratio (HR) = 3.97; p < 0.006) or 16q loss (HR = 2.41; p = 0.038). Our results highlight the importance of genomic studies in different MB histological variants and indicate a genotype-phenotype correlation.
authors.affiliation: Translational Oncopathology, National Cancer Research Institute (IST), Genoa, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Coco
authors.forename: Francesca
authors.initials: F
authors.lastname: Valdora
authors.forename: Stefano
authors.initials: S
authors.lastname: Bonassi
authors.forename: Paola
authors.initials: P
authors.lastname: Scaruffi
authors.forename: Sara
authors.initials: S
authors.lastname: Stigliani
authors.forename: André
authors.initials: A
authors.lastname: Oberthuer
authors.forename: Frank
authors.initials: F
authors.lastname: Berthold
authors.forename: Immacolata
authors.initials: I
authors.lastname: Andolfo
authors.forename: Tiziana
authors.initials: T
authors.lastname: Servidei
authors.forename: Riccardo
authors.initials: R
authors.lastname: Riccardi
authors.forename: Eleonora
authors.initials: E
authors.lastname: Basso
authors.forename: Achille
authors.initials: A
authors.lastname: Iolascon
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Tonini
mesh_terms: D000293:Adolescent; D002528:Cerebellar Neoplasms / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology*; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008527:Medulloblastoma / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology*; D015999:Multivariate Analysis; D016019:Survival Analysis