Recurrent DGCR8, DROSHA, and SIX Homeodomain Mutations in Favorable Histology Wilms Tumors

Amy L. Walz, Ariadne Ooms, Samantha Gadd, Daniela S. Gerhard, Malcolm A. Smith, Jamie M. GuidryAuvil, Daoud Meerzaman, Qing Rong Chen, Chih Hao Hsu, Chunhua Yan, Cu Nguyen, Ying Hu, Reanne Bowlby, Denise Brooks, Yussanne Ma, Andrew J. Mungall, Richard A. Moore, Jacqueline Schein, Marco A. Marra, Vicki HuffJeffrey S. Dome, Yueh Yun Chi, Charles G. Mullighan, Jing Ma, David A. Wheeler, Oliver A. Hampton, Nadereh Jafari, Nicole Ross, Julie M. Gastier-Foster, Elizabeth J. Perlman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

180 Scopus citations


We report the most common single-nucleotide substitution/deletion mutations in favorable histology Wilms tumors (FHWTs) to occur within SIX1/. 2 (7% of 534 tumors) and microRNA processing genes (miRNAPGs) DGCR8 and DROSHA (15% of 534 tumors). Comprehensive analysis of 77 FHWTs indicates that tumors with SIX1/. 2 and/or miRNAPG mutations show a pre-induction metanephric mesenchyme gene expression pattern and are significantly associated with both perilobar nephrogenic rests and 11p15 imprinting aberrations. Significantly decreased expression of mature Let-7a and the miR-200 family (responsible for mesenchymal-to-epithelial transition) in miRNAPG mutant tumors is associated with an undifferentiated blastemal histology. The combination of SIX and miRNAPG mutations in the same tumor is associated with evidence of RAS activation and a higher rate of relapse and death.

Original languageEnglish (US)
Pages (from-to)286-297
Number of pages12
JournalCancer cell
Issue number2
StatePublished - Feb 9 2015

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Cell Biology


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