title: Genomic profiling by whole-genome single nucleotide polymorphism arrays in Wilms tumor and association with relapse.
abstract: Despite the excellent survival rate of Wilms tumor (WT) patients, only approximately one-half of children who suffer tumor recurrence reach second durable remission. This underlines the need for novel markers to optimize initial treatment. We investigated 77 tumors using Illumina 370CNV-QUAD genotyping BeadChip arrays and compared their genomic profiles to detect copy number (CN) abnormalities and allelic ratio anomalies associated with the following clinicopathological variables: relapse (yes vs. no), age at diagnosis (≤ 24 months vs. >24 months), and disease stage (low stage, I and II, vs. high stage, III and IV). We found that CN gains at chromosome region 1q21.1-q31.3 were significantly associated with relapse. Additional genetic events, including allelic imbalances at chromosome arms 1p, 1q, 3p, 3q, and 14q were also found to occur at higher frequency in relapsing tumors. Interestingly, allelic imbalances at 1p and 14q also showed a borderline association with higher tumor stages. No genetic events were found to be associated with age at diagnosis. This is the first genome wide analysis with single nucleotide polymorphism (SNP) arrays specifically investigating the role of genetic anomalies in predicting WT relapse on cases prospectively enrolled in the same clinical trial. Our study, besides confirming the role of 1q gains, identified a number of additional candidate genetic markers, warranting further molecular investigations.
authors.affiliation: Department of Preventive and Predictive Medicine, Unit of Molecular Bases of Genetic Risk and Genetic Testing, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. daniela.perotti@istitutotumori.mi.it
authors.forename: Daniela
authors.initials: D
authors.lastname: Perotti
authors.forename: Filippo
authors.initials: F
authors.lastname: Spreafico
authors.forename: Federica
authors.initials: F
authors.lastname: Torri
authors.forename: Beatrice
authors.initials: B
authors.lastname: Gamba
authors.forename: Pio
authors.initials: P
authors.lastname: D'Adamo
authors.forename: Sara
authors.initials: S
authors.lastname: Pizzamiglio
authors.forename: Monica
authors.initials: M
authors.lastname: Terenziani
authors.forename: Serena
authors.initials: S
authors.lastname: Catania
authors.forename: Paola
authors.initials: P
authors.lastname: Collini
authors.forename: Marilina
authors.initials: M
authors.lastname: Nantron
authors.forename: Andrea
authors.initials: A
authors.lastname: Pession
authors.forename: Maurizio
authors.initials: M
authors.lastname: Bianchi
authors.forename: Paolo
authors.initials: P
authors.lastname: Indolfi
authors.forename: Paolo
authors.initials: P
authors.lastname: D'Angelo
authors.forename: Franca
authors.initials: F
authors.lastname: Fossati-Bellani
authors.forename: Paolo
authors.initials: P
authors.lastname: Verderio
authors.forename: Fabio
authors.initials: F
authors.lastname: Macciardi
authors.forename: Paolo
authors.initials: P
authors.lastname: Radice
mesh_terms: D000293:Adolescent; D022981:Allelic Imbalance; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D056915:DNA Copy Number Variations; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012008:Recurrence; D009396:Wilms Tumor / Q000235:genetics*
chemical_list: D005819:Genetic Markers