title: 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: 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.
authors: Amy L
authors: AL
authors: Walz
authors: Department of Pathology, Josephine Nefkens Institute, Erasmus Medical Center, Rotterdam CA 3000, the Netherlands.
authors: Ariadne
authors: A
authors: Ooms
authors: 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.
authors: Samantha
authors: S
authors: Gadd
authors: Office of Cancer Genomics, National Cancer Institute, Bethesda, MD 20892, USA.
authors: Daniela S
authors: DS
authors: Gerhard
authors: Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD 20892, USA.
authors: Malcolm A
authors: MA
authors: Smith
authors: Jaime M
authors: JM
authors: Guidry Auvil
authors: Office of Cancer Genomics, National Cancer Institute, Bethesda, MD 20892, USA.
authors: Jamie M
authors: JM
authors: Guidry Auvil
authors: Center for Biomedical Informatics and Information Technology, National Cancer Institute, Bethesda, MD 20892, USA.
authors: Daoud
authors: D
authors: Meerzaman
authors: Center for Biomedical Informatics and Information Technology, National Cancer Institute, Bethesda, MD 20892, USA.
authors: Qing-Rong
authors: QR
authors: Chen
authors: Center for Biomedical Informatics and Information Technology, National Cancer Institute, Bethesda, MD 20892, USA.
authors: Chih Hao
authors: CH
authors: Hsu
authors: Center for Biomedical Informatics and Information Technology, National Cancer Institute, Bethesda, MD 20892, USA.
authors: Chunhua
authors: C
authors: Yan
authors: Center for Biomedical Informatics and Information Technology, National Cancer Institute, Bethesda, MD 20892, USA.
authors: Cu
authors: C
authors: Nguyen
authors: Center for Biomedical Informatics and Information Technology, National Cancer Institute, Bethesda, MD 20892, USA.
authors: Ying
authors: Y
authors: Hu
authors: Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC V5Z 4S6, Canada.
authors: Reanne
authors: R
authors: Bowlby
authors: Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC V5Z 4S6, Canada.
authors: Denise
authors: D
authors: Brooks
authors: Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC V5Z 4S6, Canada.
authors: Yussanne
authors: Y
authors: Ma
authors: Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC V5Z 4S6, Canada.
authors: Andrew J
authors: AJ
authors: Mungall
authors: Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC V5Z 4S6, Canada.
authors: Richard A
authors: RA
authors: Moore
authors: Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC V5Z 4S6, Canada.
authors: Jacqueline
authors: J
authors: Schein
authors: 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.
authors: Marco A
authors: MA
authors: Marra
authors: Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Vicki
authors: V
authors: Huff
authors: Division of Pediatric Hematology/Oncology, Children's National Medical Center, Washington, DC 20010, USA.
authors: Jeffrey S
authors: JS
authors: Dome
authors: Department of Biostatistics, University of Florida, Gainesville, FL 32610, USA.
authors: Yueh-Yun
authors: YY
authors: Chi
authors: Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Charles G
authors: CG
authors: Mullighan
authors: Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Jing
authors: J
authors: Ma
authors: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
authors: David A
authors: DA
authors: Wheeler
authors: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
authors: Oliver A
authors: OA
authors: Hampton
authors: Center for Genetic Medicine, Northwestern University, Chicago, IL 60611, USA.
authors: Nadereh
authors: N
authors: Jafari
authors: Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Ohio State University College of Medicine, Columbus, OH 43205, USA.
authors: Nicole
authors: N
authors: Ross
authors: Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Ohio State University College of Medicine, Columbus, OH 43205, USA.
authors: Julie M
authors: JM
authors: Gastier-Foster
authors: 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.
authors: Elizabeth J
authors: EJ
authors: Perlman
mesh_terms: D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D016601:RNA-Binding Proteins / Q000235:genetics*; D043244:Ribonuclease III / Q000235:genetics*; D009396:Wilms Tumor / Q000235:genetics* / Q000473:pathology
chemical_list: C474043:DGCR8 protein, human; D018398:Homeodomain Proteins; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C099236:SIX1 protein, human; C484762:SIX2 protein, human; C487931:mirnlet7 microRNA, human; C517918:DROSHA protein, human; D043244:Ribonuclease III