title: WT1 gene analysis in sporadic early-onset and bilateral wilms tumor patients without associated abnormalities.
abstract: The WT1 gene is responsible for two different genetic conditions characterized by genitourinary anomalies and susceptibility to Wilms tumor (WT): the WAGR syndrome and the Denys-Drash syndrome. Although only rarely, WT1 constitutional mutations have been reported also in WT patients without congenital defects. Due to the high survival rates that characterize the disease, these individuals must be identified and counseled in relation to their risk to transmit a cancer-predisposing genetic lesion to their offspring. Recently, tumor bilaterality and early age of onset have been suggested to be risk factors for carrying germline WT1 mutations. The authors investigated 20 patients with sporadic WT, without evidence of congenital abnormalities, diagnosed before 2 years of age and/or with bilateral presentation, for the occurrence of WT1 mutations. Southern blot analyses identified homozygous whole-gene or intragenic deletions at the tumor level in three cases. However, none of the identified alterations was found to be present at the germline level. In addition, no mutation in the coding exons and flanking sequences of WT1 was detected in the remaining 17 cases. These results suggest that early age of diagnosis and bilaterality are not by themselves efficient predictors of germline WT1 alterations in WT patients without associated abnormalities.
authors.affiliation: Department of Experimental Oncology and Laboratories, Istituto Nazionale Tumori, 20133 Milan, Italy. daniela.perotti@istitutotumori.mi.it
authors.forename: Daniela
authors.initials: D
authors.lastname: Perotti
authors.forename: Patrizia
authors.initials: P
authors.lastname: Mondini
authors.forename: Monica
authors.initials: M
authors.lastname: Terenziani
authors.forename: Filippo
authors.initials: F
authors.lastname: Spreafico
authors.forename: Paola
authors.initials: P
authors.lastname: Collini
authors.forename: Franca
authors.initials: F
authors.lastname: Fossati-Bellani
authors.forename: Paolo
authors.initials: P
authors.lastname: Radice
mesh_terms: D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D007223:Infant; D007680:Kidney Neoplasms / Q000235:genetics*; D019656:Loss of Heterozygosity; D008297:Male; D025721:WT1 Proteins / Q000235:genetics*; D009396:Wilms Tumor / Q000235:genetics*
chemical_list: D025721:WT1 Proteins