title: Genomic imbalances pinpoint potential oncogenes and tumor suppressors in Wilms tumors.
abstract: BACKGROUND
  Wilms tumor (WT) has a not completely elucidated pathogenesis. DNA copy number alterations (CNAs) are common in cancer, and often define key pathogenic events. The aim of this work was to investigate CNAs in order to disclose new candidate genes for Wilms tumorigenesis.
  
  
  RESULTS
  Array-CGH of 50 primary WTs without pre-chemotherapy revealed a few recurrent CNAs not previously reported, such as 7q and 20q gains, and 7p loss. Genomic amplifications were exclusively detected in 3 cases of WTs that later relapsed, which also exhibited an increased frequency of gains affecting a 16.2 Mb 1q21.1-q23.2 region, losses at 11p, 11q distal, and 16q, and WT1 deletions. Conversely, aneuploidies of chromosomes 13 and 19 were found only in WTs without further relapse. The 1q21.1-q23.2 gain associated with WT relapse harbours genes such as CHD1L, CRABP2, GJA8, MEX3A and MLLT11 that were found to be over-expressed in WTs. In addition, down-regulation of genes encompassed by focal deletions highlighted new potential tumor suppressors such as CNKSR1, MAN1C1, PAQR7 (1p36), TWIST1, SOSTDC1 (7p14.1-p12.2), BBOX and FIBIN (11p13), and PLCG2 (16q).
  
  
  CONCLUSIONS
  This study confirmed the presence of CNAs previously related to WT and characterized new CNAs found only in few cases. The later were found in higher frequency in relapsed cases, suggesting that they could be associated with WT progression.
authors.affiliation: International Research Center, AC Camargo Cancer Center, São Paulo, Brazil.|Institute of Biosciences, University of São Paulo, São Paulo, Brazil.
authors.forename: A C V
authors.initials: ACV
authors.lastname: Krepischi
authors.affiliation: International Research Center, AC Camargo Cancer Center, São Paulo, Brazil.|Brazilian Biosciences National Laboratory, National Center for Research in Energy and Materials, Campinas, São Paulo, Brazil.
authors.forename: M
authors.initials: M
authors.lastname: Maschietto
authors.affiliation: International Research Center, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: E N
authors.initials: EN
authors.lastname: Ferreira
authors.affiliation: Institute of Biosciences, University of São Paulo, São Paulo, Brazil.
authors.forename: A G
authors.initials: AG
authors.lastname: Silva
authors.affiliation: Institute of Biosciences, University of São Paulo, São Paulo, Brazil.
authors.forename: S S
authors.initials: SS
authors.lastname: Costa
authors.affiliation: Department of Surgical and Investigative Pathology, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: I W
authors.initials: IW
authors.lastname: da Cunha
authors.affiliation: International Research Center, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: B D F
authors.initials: BDF
authors.lastname: Barros
authors.affiliation: Alberta Health Services, Cancer Control Alberta, Alberta, Canada.
authors.forename: P E
authors.initials: PE
authors.lastname: Grundy
authors.affiliation: Institute of Biosciences, University of São Paulo, São Paulo, Brazil.
authors.forename: C
authors.initials: C
authors.lastname: Rosenberg
authors.affiliation: International Research Center, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: D M
authors.initials: DM
authors.lastname: Carraro
keywords: 1q21.1-q23.2 gain; Array-CGH; CNA; Copy number alteration; Relapse; Wilms tumor