WT1 mutations and single nucleotide polymorphism rs16754 analysis of patients with pediatric acute myeloid leukemia in a Chinese population
Center for Clinical Molecular Medicine, Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Children's Hospital, Chongqing Medical University , Chongqing , China. Leukemia & lymphoma
(Impact Factor: 2.89).
04/2012; 53(11):2195-204. DOI: 10.3109/10428194.2012.685732
Abstract Acute myeloid leukemia (AML) is relatively rare in children. Somatic mutations including the single nucleotide polymorphism (SNP) rs16754 in Wilms tumor 1 gene (WT1) and their prognostic relevance in pediatric AML have not been studied in Chinese populations. We analyzed WT1 mutations and rs16754 genotypes in a cohort of 86 patients with de novo pediatric AML in a Chinese population. We detected WT1 mutations in approximately 20% of the patients. Most of the mutations identified were deletions and insertions clustered in exons 7 and 9. No differences were observed with respect to overall survival and relapse-free survival between patients with and without WT1 mutations. The analysis of rs16754 in WT1 exon 7 revealed G as the major allele. Patients with the rs16754(GG) genotype had improved overall survival (p =0.020) and relapse-free survival (p =0.025) compared with those with either rs16754(GA) or rs16754(AA). Moreover, better overall survival (p =0.044) and relapse-free survival (p =0.068) were observed among patients with wild-type CEBPA with rs16754(GG) compared with those carrying rs16754(GA/AA).
Available from: Raviprakash T. Sitaram
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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.
Available from: informahealthcare.com
Available from: Xiaowei Qi
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ABSTRACT: Wilms' tumor gene 1 (WT1) single nucleotide polymorphism (SNP), rs16754, has been considered as an independent prognostic factor in patients with acute myeloid leukemia and renal cell carcinoma. However, its biological role in breast cancer has not been reported. To test whether WT1 SNPs can be used as a molecular marker in order to improve the risk stratification of breast cancer, we performed a case-control study including 709 female sporadic breast cancer patients and 749 female healthy control subjects in the Southeast China. Five WT1 SNPs (rs16754, rs3930513, rs5030141, rs5030317, rs5030320) were selected and determined by polymerase chain reaction-ligase detection reaction to assess their associations with breast cancer risk. Results showed the distributions of the alleles of these WT1 SNPs were consistent with data from Chinese population as suggested by the International HapMap Project. Individuals with the minor alleles of rs16754, rs5030317 and rs5030320 showed a significant decrease of breast cancer risk in codominant model (OR = 0.6370, 95% CI: 0.4260-0.9520 for rs16754; OR = 0.5940, 95% CI: 0.3890-0.9070 for rs5030317; OR = 0.5870, 95% CI: 0.3850-0.8960 for 5030320, respectively) and recessive model. Stratified analyses showed the protective effects were more evident in the subjects with age ≤ 50 years or in pre-menopausal status. To explore the potential mechanism, we conducted bioinformatics genotype-phenotype correlation analysis, and found that the mRNA expression level for homozygous rare allele of WT1 gene was lower than that in wild-type and heterozygous group (P = 0.0021) in Chinese population. In summary, our findings indicated that minor alleles of rs16754, rs5030317 and rs5030320 are associated with reduced risk of breast cancer, suggesting that WT1 SNPs may be a potential biomarker of individualized prediction of susceptibility to breast cancer. However, large prospective and molecular epidemiology studies are needed to verify this correlation and clarify its underlying mechanisms.
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