Wilms tumor is the most common childhood kidney cancer. Here we report the whole-exome sequencing of 44 Wilms tumors, identifying missense mutations in the microRNA (miRNA)-processing enzymes DROSHA and DICER1 and novel mutations in MYCN, SMARCA4 and ARID1A. Examination of tumor miRNA expression, in vitro processing assays, and genomic editing in human cells demonstrate that DICER1 and DROSHA mutations influence miRNA processing through distinct mechanisms. DICER1 RNase IIIB mutations preferentially impair processing of miRNAs deriving from the 5′ arm of pre-miRNA hairpins, while DROSHA RNase IIIB mutations globally inhibit miRNA biogenesis through a dominant-negative mechanism. Both DROSHA and DICER1 mutations impair expression of tumor-suppressing miRNAs including the let-7 family, important regulators of MYCN, LIN28 and other Wilms tumor oncogenes. These results provide new insights into the mechanisms through which mutations in miRNA biogenesis components reprogram miRNA expression in human cancer and suggest that these defects define a distinct subclass of Wilms tumors.

Laparoscopic retroperitoneal lymph node dissection (RPLND) has been shown to be safe and effective in appropriately selected pediatric and adolescent patients with paratesticular rhabdomyosarcoma (RMS) and testicular germ-cell tumors (T-GCT). While the use of robot-assisted laparoscopy has expanded rapidly in many areas, there are very limited reports of its use with RPLND. We present two cases of adolescents who were treated using robot-assisted laparoscopic RPLND (R-RPLND)-one with paratesticular RMS (PT-RMS) and one with testicular GCT (T-GCT)-with good outcomes and low morbidity.