title: WT1, WTX and CTNNB1 mutation analysis in 43 patients with sporadic Wilms'             tumor.
abstract: Wilms' tumor (WT) is a heterogeneous neoplasia characterized by a number             of genetic abnormalities, involving tumor suppressor genes, oncogenes and genes             related to the Wnt signaling pathway. Somatic biallelic inactivation of WT1 is             observed in 5-10% of sporadic WT. Somatic mutations in exon 3 of CTNNB1, which             encodes β-catenin, were initially observed in 15% of WT. WTX encodes a protein             that negatively regulates the Wnt/β-catenin signaling pathway and mediates the             binding of WT1. In this study, we screened germline and somatic mutations in selected             regions of WT1, WTX and CTNNB1 in 43 WT patients. Mutation analysis of WT1 identified             two single-nucleotide polymorphisms, one recurrent nonsense mutation (p.R458X)             in a patient with proteinuria but without genitourinary findings of Denys-Drash             syndrome (DDS) and one novel missense mutation, p.C428Y, in a patient with Denys-Drash             syndrome phenotype. WT1 SNP rs16754A>G (R369R) was observed in 17/43 patients,             and was not associated with significant difference in age at diagnosis distribution,             or with 60-month overall survival rate. WTX mutation analysis identified five             sequence variations, two synonymous substitutions (p.Q1019Q and p.D379D), a non-synonymous             mutation (p.F159L), one frameshift mutation (p.157X) and a novel missense mutation,             p.R560W. Two sequence variations in CTNNB1 were identified, p.T41A and p.S45C.             Overall survival of bilateral cases was significantly lower (p=0.005). No difference             was observed when survival was analyzed among patients with WT1 or with WTX mutations.             On the other hand, the survival of two patients with the CTNNB1 p.T41A mutation             was significantly lower (p=0.000517) than the average.
authors.affiliation: Department of Genetics, Federal University of Rio de Janeiro,                     Rio de Janeiro, RJ, 21944‑970, Brazil.
authors.forename: Leila C A
authors.initials: LC
authors.lastname: Cardoso
authors.forename: Kelly R L
authors.initials: KR
authors.lastname: De Souza
authors.forename: Adriana Helena
authors.initials: AH
authors.lastname: De O Reis
authors.forename: Raissa Coelho
authors.initials: RC
authors.lastname: Andrade
authors.forename: Alberto C
authors.initials: AC
authors.lastname: Britto
authors.forename: Maria A F D
authors.initials: MA
authors.lastname: De Lima
authors.forename: Anna C E
authors.initials: AC
authors.lastname: Dos Santos
authors.forename: Paulo S
authors.initials: PS
authors.lastname: De Faria
authors.forename: Sima
authors.initials: S
authors.lastname: Ferman
authors.forename: Héctor N
authors.initials: HN
authors.lastname: Seuánez
authors.forename: Fernando R
authors.initials: FR
authors.lastname: Vargas
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007680:Kidney Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D025721:WT1 Proteins / Q000235:genetics*; D009396:Wilms Tumor / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D051176:beta Catenin / Q000235:genetics*
chemical_list: C517118:AMER1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D025521:Tumor Suppressor Proteins; D025721:WT1 Proteins; C583751:WT1 protein, human; D051176:beta Catenin