MOLECULAR CHARACTERIZATION OF CHEMO SENSITIVE AND CHEMO RESISTANT WILMS` TUMOR BLASTEMAL TYPE USING SAGE LIBRARIES Piccoli, FS1; de Camargo, B2; de Caballero, OLSD1; Soares, FA3; Sredni, ST3; Silva Jr, WA4; dos Santos, ARD4; Zanette, DL4; Brentani, H5; Camargo, LP5; Vettore, AL1
1Ludwig Institute for Cancer Research, SP; 2Depart. of Pediatrics, Hospital do Cancer A.C. Camargo, SP; 3Depart. of Pathology, Hospital do Cancer A.C. Camargo, SP; 4Center for Cell Therapy and Regional Blood Center, USP Ribeirao Preto, SP; 5Laboratory of Bioinformatics of Hospital do Cancer A.C. Camargo, SP
Wilms’ Tumor (WT), the most common childhood renal cancer, is an embryonal tumor composed by blastemal, stromal and epithelial histological components. As more than 80% of the WT can be cured, the current treatment protocols aim to decrease therapy aggressiveness for patients undergoing good prognosis and to adjust the most severe treatment for the group of poor responders. The blastemal component (BC) usually presents great sensibility to chemotherapy (CT) being correlated to good prognosis. However, in some cases, it is found to be resistant to CT, being associated to most therapeutic failures and bad prognosis. Thus, the identification, at diagnosis, of chemo-sensitive (CS) and chemo-resistant (CR) tumors becomes of great importance for an early implementation of a more individualized therapeutics. The objective of this study is to identify molecular markers of chemotherapy response for WT using SAGE analysis. Two SAGE libraries were constructed from WTBC tissues originated from tumors characterized as CS and CR. Data from a second CR WTBC library, constructed by another group, were added to the comparative analysis. After a bioinformatic and gene function analyses, were selected 11 over-expressed (GNG2, GNA13, CRABP2, GAS6, RNF130, IGFBP4, SPARC, MAT2A, RAP1B, HSPA8 and SERPINH1) and 3 under-expressed genes (MCM7, FSCN1 and EI24) in CR tumors, involved in different biologic processes that could be related to CT response as apoptosis, cytoskeleton maintenance, DNA replication and repair, cell signaling and responsiveness to Retinoic Acid. The differential expression of these genes was validated by Real-time RT-PCR in WT samples with and without tumor recurrence. The selected genes can be seen as candidates for molecular markers relevant for prediction of CT response and/or may represent targets for drug development, which may improve the prognosis of WT patients. Supported by FAPESP
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