| Wilms tumor is a pediatric kidney tumor and is the most common solid tumor in children. Presumably, Wilms tumors arise from nephrogenic rests, microscopic foci of residual fetal kidney that persists after the maturation of the kidney. Many Wilms tumors have been linked to the short arm of chromosome 11. This region of the genome contains a number of imprinted genes; genes with preferential expression from one parental allele. Although common mutations in genes from 11p15 have not been found, several epigenetic changes have been discovered. One of the most common defects in Wilms tumors is loss of imprinting (LOI), resulting in biallelic expression of the insulin-like growth factor-II (IGF2) gene, an autocrine growth factor. Additionally, Wilms tumors often have loss of heterozygosity (LOH) of the short arm of chromosome 11, with preferential loss of the maternal chromosome. The effect of genetic and epigenetic changes, including LOI, LOH, and mutations, the specific histopathological characteristics of each tumor, and the normal function and role in tumorigenesis of a gene can be determined by a careful comparison of these characteristics with the level of gene expression. To accomplish this, I examined the expression level of eight genes and two control genes in a set of 98 Wilms tumors, 98 matched normal kidneys, and 24 fetal kidneys using Real-Time Quantitative Polymerase Chain Reaction. This work resulted in a large database of information on Wilms tumors, including gene expression levels, genetic and epigenetic information, and pathological characteristics. Several significant observations were made from these data and analysis. The results reveal the relative expression level profile of each gene in normal and fetal kidney and in Wilms tumor. The expression level of several genes in close physical proximity on the chromosome correlated in particular tissues. In addition, epigenetic changes were found to effect gene expression levels and to be specifically associated with distinct classifications of Wilms tumors. These groups of tumors were found to have changes in expression level corresponding to their epigenetic changes. These data resulted in a new model of Wilms tumorigenesis involving epigenetic alterations, complementing the classic genetic model of Wilms tumor. |
