MOLECULAR CHARACTERIZATION AND CLINICAL MANIFESTATIONS IN PATIENTS WITH WILMS TUMOR

INTRODUCTION AND OBJECTIVE: Wilms Tumor (WT) is the most common renal neoplasm in childhood, accounting for approximately 7% of all pediatric tumors. On average, 4-year survival rate in high-income countries is 80%, in contrast, it is only 50% in low-income countries. Bilateral or multicentric tumors are seen in 12.5% of patients and, some cases, might have other malformations and anomalies connected to them, suggesting an hereditary form of disease. This study aims to sequence the WT1 and WTX genes in patients referred to the Instituto Nacional do Câncer’s genetic counseling service in order to determine the prevalence of carriers of deleterious variants in these genes and to describe the clinicopathological traits and clinical manifestations associated with WT. MATERIAL AND METHOD: This study is part of the project "Inherited Susceptibility to Solid Cancers in Brazilian Pediatric Patients", approved by the CEP 70458323.3.0000.5274. All patients referred to the INCA’s genetic counseling service since January 2014 with clinical or histological diagnosis of WT were eligible to participate in this ambispective study. Data regarding clinicopathological features and family history of cancer will be gathered from their medical records. Genomic DNA was extracted from peripheral blood using the saline extraction method. The coding regions of the WT1 and WTX genes were amplified by PCR. Sanger method was used to sequence the purified PCR products, and ChromasPro software was used to compare the results with reference sequences. RESULTS AND CONCLUSION: To date, 49 probands (21 females and 28 males) have consented to participate in this project. The average age at diagnosis was 2 years and 3 months. Six individuals were diagnosed with bilateral tumors, 26 with unilateral tumors and for 17 there is no information available. Sixteen patients had WT1 gene partially sequenced, and 4 benign or likely benign variants were found: 1) c.887+16G>A, identified in heterozygosity in three patients; 2) c.785-195C>A, found heterozygous in three patients and homozygous in one patient and; 3) c.785-57C>T, found in two patients in heterozygosity; 4) c.1122A>G (p.Arg374=), found heterozygous in five patients. It is necessary to complete the collection of data on clinical manifestations, as well as sequencing in order to establish the phenotypic and genotypic profile of patients treated at the institution.