Penetrance of WT1 and WT2 Gene Mutation and Loss of Heterozygosity in Wilms tumors in Indian Population

Abstract

Ajit Kumar Saxena, Veena Singh, Vijayendra Kumar, Pritanjali Singh, Meenakshi Tiwari, Ramanuj Kumar and Chandan Kumar Singh

Wilms tumor is a nephroblastoma of pediatric age group and heterogeneous in nature. WT1 and WT2 gene mutations are involved in onset of tumorigenesis in syndromic and non syndromic cases of Wilms tumor. Present study has been designed with aim to evaluate the frequency of WT1 and WT2 gene mutation, loss of heterozygosity (LOH) and DNA copy number variation (CNV) in clinically diagnosed cases of Wilms tumor using RT-PCR based analysis. Findings reveals that there was vast difference in the mutation frequency between WT1 (7.5%) and WT2 (17.5) gene, and statistical analysis shows significant difference (p < 0.05) in WT2 mutation and calculated value of C.I. varies between 0.886-1.990 at 95% with odd ratio (7.52). Interestingly, the frequency of LOH (loss of heterozygosity and DNA copy number variations (CNVs) shows significant difference (p < 0.01), suggesting increase of genetic susceptibility and penetrance of gene in proband of the family tumor resulting increase of risk factor after using three different microsatellite DNA markers (DS11S935, DS11S904 and DS11S1363). Genetic heterogenecity were also observed by calculating Tm values, between cases and controls (GAPDH), and C.I. varies between 0.292 - 2.270 at 95% with O.R = 0.54 in D11S1363 and maximum value of C.I. was 1.165-2.165 at 95% with O.R = 0.50 in D11S1905 and the p = 0.194 & p = 0.522 respectively, between cases and controls..

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