title: Single nucleotide polymorphisms in the Wilms' tumour gene 1 in clear cell renal cell carcinoma.
abstract: The Wilms' tumour gene 1 (WT1) single nucleotide polymorphism (SNP) rs16754 has recently been described as an independent prognostic factor in acute myeloid leukaemia (AML) patients. It is of great interest to test whether WT1 SNPs can be used as a molecular marker in other cancer types in order to improve risk and treatment stratification. We performed sequencing analysis on all 10 exons of the WT1 gene in a total of 182 patients with clear cell renal cell carcinoma (ccRCC). Six different SNPs were identified, in descending order for minor allele frequency: rs2234582, rs16754, rs1799925, rs5030315, rs2234583, and rs2234581. At least one minor allele for WT1 SNP was identified in 61% of ccRCC patients. In the entire study population, only 6% carried two copies of the minor allele. The genotypes of WT1 SNPs in 78 tumour-free kidney tissue specimens were found to be in 95% concordance with corresponding tumour samples. No correlation was observed between WT1 SNP genotypes and RNA expression level. WT1 SNP genotypes did not associate with clinical and pathological characteristics. We found favourable outcomes associated with the homozygous minor allele for WT1 SNP. However, SNP genotypes did not show to be of prognostic significance when comparing wild-type versus homozygous or heterozygous for the minor allele in the entire cohort. None of the previously reported WT1 mutations in AML was found in the present study. A novel WT1 missense mutation was identified in only one patient. Our data suggest that common WT1 mutations are not involved in ccRCC. Due to too few cases harbouring the homozygous minor allele, the prognostic impact needs to be verified in larger study populations.
authors.affiliation: Department of Medical Biosciences, Clinical Chemistry, Umeå University, Umeå, Sweden.
authors.forename: Xingru
authors.initials: X
authors.lastname: Li
authors.forename: Sihan
authors.initials: S
authors.lastname: Wang
authors.forename: Raviprakash T
authors.initials: RT
authors.lastname: Sitaram
authors.forename: Charlotta
authors.initials: C
authors.lastname: Andersson
authors.forename: Börje
authors.initials: B
authors.lastname: Ljungberg
authors.forename: Aihong
authors.initials: A
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005787:Gene Frequency; D016162:Genes, Wilms Tumor; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013548:Sweden