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Cancer Cell. 2015 Feb 9;27(2):286-97. doi: 10.1016/j.ccell.2015.01.003.

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

Author information

1
Division of Hematology-Oncology and Transplantation, Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University's Feinberg School of Medicine, Chicago, IL 60611, USA.
2
Department of Pathology, Josephine Nefkens Institute, Erasmus Medical Center, Rotterdam CA 3000, the Netherlands.
3
Department of Pathology and Laboratory Medicine, Lurie Children's Hospital, Northwestern University's Feinberg School of Medicine and Robert H. Lurie Cancer Center, Chicago, IL 60611, USA.
4
Office of Cancer Genomics, National Cancer Institute, Bethesda, MD 20892, USA.
5
Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD 20892, USA.
6
Center for Biomedical Informatics and Information Technology, National Cancer Institute, Bethesda, MD 20892, USA.
7
Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC V5Z 4S6, Canada.
8
Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC V5Z 4S6, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, BC V6H 3N1, Canada.
9
Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
10
Division of Pediatric Hematology/Oncology, Children's National Medical Center, Washington, DC 20010, USA.
11
Department of Biostatistics, University of Florida, Gainesville, FL 32610, USA.
12
Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
13
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
14
Center for Genetic Medicine, Northwestern University, Chicago, IL 60611, USA.
15
Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Ohio State University College of Medicine, Columbus, OH 43205, USA.
16
Department of Pathology and Laboratory Medicine, Lurie Children's Hospital, Northwestern University's Feinberg School of Medicine and Robert H. Lurie Cancer Center, Chicago, IL 60611, USA. Electronic address: eperlman@luriechildrens.org.

Erratum in

  • Cancer Cell. 2015 Mar 9;27(3):426. Guidry Auvil, Jamie M [corrected to Guidry Auvil, Jaime M].

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.

PMID:
25670082
PMCID:
PMC4800737
DOI:
10.1016/j.ccell.2015.01.003
[Indexed for MEDLINE]
Free PMC Article

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