Gene expression of distinct histological components of Wilms tumor analyzed under the perspective of kidney development

Gene expression analyses through cDNA microarray of unique Wilms tumor (WT) histological components, blastema (BL), epithelia (EP) and stroma (ST), from different patients were performed and compared with non-neoplastic mature and pool of fetal kidney (FK). We used a customized cDNA array containing 4 608 human genes and demonstrated that BL had over representation of genes with similar expression behavior to the earliest stage of normal renal development. Moreover, since WT is a result of loss of developmental control and gain of tumorigenic potential in a successive way, herein we identified genes whose expression level is altered during the kidney development and also in WT and classified as WT-kidney development set. From this set, a smaller group of 36 differentially expressed genes was derived, which was enriched by genes involved in signal transduction, such as APC, BZRP, MET, PLAU, GPR35 and TRADD. An over representation of genes belonging to the WNT signaling pathway were observed. Immunostaining assays of APC and beta-catenin were carried out in 108 specimens showing differential labeling localization in WT. Altogether our data show molecular evidences confirming the recapitulation of embryonic kidney by WT components and strongly suggest that the WNT signaling pathway plays a crucial role in Wilms tumorigenesis. Keywords: Wilms tumor, cDNA microarray, Histological components, WNT signaling pathway We performed gene expression analyses by customized cDNA array using dye swap with reference design, of unique histological components of Wilms tumors (6 blastemal, 6 epithelial and 3 stromal components) from different patients and compared to 3 normal mature and a pool of fetal kidneys (triplicate). These differentially expressed lists were compared with available data of differentially expressed genes during kidney development.