Recurrent DGCR8, DROSHA, and SIX homeodomain mutations in favorable histology Wilms tumors.

Abstract

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.

• Authors: Amy L Walz, Ariadne Ooms, Samantha Gadd, Daniela S Gerhard, Malcolm A Smith, Jaime M Guidry Auvil, Jamie M Guidry Auvil, 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 Huff, Jeffrey 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
• Journal: Cancer cell (Cancer Cell) Vol. 27 Issue 2 Pg. 286-97 (Feb 09 2015) ISSN: 1878-3686 [Electronic] United States
• PMID: 25670082 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• DGCR8 protein, human
• Homeodomain Proteins
• MicroRNAs
• Nerve Tissue Proteins
• RNA-Binding Proteins
• SIX1 protein, human
• SIX2 protein, human
• mirnlet7 microRNA, human
• DROSHA protein, human
• Ribonuclease III

Topics

• Gene Expression Regulation, Neoplastic
• Homeodomain Proteins (genetics)
• Humans
• Loss of Heterozygosity (genetics)
• MicroRNAs (genetics)
• Mutation
• Neoplasm Recurrence, Local (genetics, pathology)
• Nerve Tissue Proteins (genetics)
• Polymorphism, Single Nucleotide
• RNA-Binding Proteins (genetics)
• Ribonuclease III (genetics)
• Wilms Tumor (genetics, pathology)