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WT1 gene was first described as a tumor suppressor, but this gene can act as an oncogene. Heterozygous variants in the WT1 gene manifest as a large variety of phenotype involving progressive renal glomerulopathy and disorders of testicular development. It was hypothesized that children with pathogenic variants in the WT1 gene submitted to kidney transplantation should be of major risk for the development of PTLD (Post-transplant lymphoproliferative disease), the most common malignancy after transplantation.
Objective: To determine the frequency of PTLD among patients with and without WT1 disorder, alerting for the possible high association between these two entities.
Data from children who had screening for variants in the WT1 gene performed, among all patients who underwent the first KT during childhood (≦18y) at Hospital Samaritano and Hospital do Rim, in Sao Paulo, were retrospectively assessed from medical database.
The frequency of PTLD diagnosis during a long-term follow-up was compared between the two groups.
WT1 gene was genotyped in 101 patients for different reasons. Pathogenic variants in the WT1 gene were detected in 6 of these patients. We detected a higher rate of 67% of PTLD diagnoses among patients with WT1-disorder, and in 4% among WT1-negative patients (p<0.001). There was no difference in the immunosuppression and PTLD screening protocol between the groups. The median follow-up was 13 and 12.4 years in WT1-positive and Wt1-negative group, respectively. The PTLD was related to Epstein-Barr virus in two WT1-positive patients. Three new variants in the WT1 gene were described.
We provide new data corroborating to the impression of higher frequency of PTLD among patients having pathogenic variant in the WT1 gene. For now, these patients should have personalized immunosuppression and accurate screening for PTLD to modify their prognosis. Moreover, the association between these two entities could bring new insights for the PTLD understanding.