title: MLLT1 YEATS domain mutations in clinically distinctive Favourable Histology Wilms tumours.
abstract: Wilms tumour is an embryonal tumour of childhood that closely resembles the developing kidney. Genomic changes responsible for the development of the majority of Wilms tumours remain largely unknown. Here we identify recurrent mutations within Wilms tumours that involve the highly conserved YEATS domain of MLLT1 (ENL), a gene known to be involved in transcriptional elongation during early development. The mutant MLLT1 protein shows altered binding to acetylated histone tails. Moreover, MLLT1-mutant tumours show an increase in MYC gene expression and HOX dysregulation. Patients with MLLT1-mutant tumours present at a younger age and have a high prevalence of precursor intralobar nephrogenic rests. These data support a model whereby activating MLLT1 mutations early in renal development result in the development of Wilms tumour.
authors.affiliation: Department of Pathology, Ann &Robert H. Lurie Children's Hospital of Chicago, Northwestern University's Feinberg School of Medicine, 225 E. Chicago Ave, Chicago, Illinosis 60611, USA.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Perlman
authors.affiliation: Department of Pathology, Ann &Robert H. Lurie Children's Hospital of Chicago, Northwestern University's Feinberg School of Medicine, 225 E. Chicago Ave, Chicago, Illinosis 60611, USA.
authors.forename: Samantha
authors.initials: S
authors.lastname: Gadd
authors.affiliation: King Abdullah University of Science and Technology, Department of Biochemistry and Molecular Biology, Division of Biological and Environmental Sciences and Engineering, Computational Bioscience Research Center, Thuwal 23955, Saudi Arabia.
authors.forename: Stefan T
authors.initials: ST
authors.lastname: Arold
authors.affiliation: King Abdullah University of Science and Technology, Department of Biochemistry and Molecular Biology, Division of Biological and Environmental Sciences and Engineering, Computational Bioscience Research Center, Thuwal 23955, Saudi Arabia.
authors.forename: Anand
authors.initials: A
authors.lastname: Radhakrishnan
authors.affiliation: Office of Cancer Genomics, National Cancer Institute, 31 Center Drive, Bethesda, Maryland 20892, USA.
authors.forename: Daniela S
authors.initials: DS
authors.lastname: Gerhard
authors.affiliation: Department of Pathology, Ann &Robert H. Lurie Children's Hospital of Chicago, Northwestern University's Feinberg School of Medicine, 225 E. Chicago Ave, Chicago, Illinosis 60611, USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Jennings
authors.affiliation: Department of Genetics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors.forename: Vicki
authors.initials: V
authors.lastname: Huff
authors.affiliation: Office of Cancer Genomics, National Cancer Institute, 31 Center Drive, Bethesda, Maryland 20892, USA.
authors.forename: Jaime M
authors.initials: JM
authors.lastname: Guidry Auvil
authors.affiliation: Office of Cancer Genomics, National Cancer Institute, 31 Center Drive, Bethesda, Maryland 20892, USA.
authors.forename: Tanja M
authors.initials: TM
authors.lastname: Davidsen
authors.affiliation: Department of Pediatrics, Division of Pediatric Hematology/Oncology, Children's National Medical Center, 111 Michigan Avenue, NW, Washington DC 20010, USA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Dome
authors.affiliation: Center for Biomedical Informatics and Information Technology, National Cancer Institute, National Institutes of Health, 9609 Medical Center Drive, Bethesda, Maryland 20892, USA.
authors.forename: Daoud
authors.initials: D
authors.lastname: Meerzaman
authors.affiliation: Center for Biomedical Informatics and Information Technology, National Cancer Institute, National Institutes of Health, 9609 Medical Center Drive, Bethesda, Maryland 20892, USA.
authors.forename: Chih Hao
authors.initials: CH
authors.lastname: Hsu
authors.affiliation: Center for Biomedical Informatics and Information Technology, National Cancer Institute, National Institutes of Health, 9609 Medical Center Drive, Bethesda, Maryland 20892, USA.
authors.forename: Cu
authors.initials: C
authors.lastname: Nguyen
authors.affiliation: Frontier Science and Technology Research Foundation, 505 S. Rosa Rd #100, Madison, Wisconsin 53719, USA.
authors.forename: James
authors.initials: J
authors.lastname: Anderson
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, British Columbia, Canada V5Z 4S6.
authors.forename: Yussanne
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, British Columbia, Canada V5Z 4S6.
authors.forename: Andrew J
authors.identifier: http://orcid.org/0000-0002-0905-2742
authors.initials: AJ
authors.lastname: Mungall
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, British Columbia, Canada V5Z 4S6.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Moore
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, British Columbia, Canada V5Z 4S6.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Marra
authors.affiliation: Department of Pathology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Mail Stop 342, Memphis, Tennessee 38105, USA.
authors.forename: Charles G
authors.identifier: http://orcid.org/0000-0002-1871-1850
authors.initials: CG
authors.lastname: Mullighan
authors.affiliation: Department of Pathology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Mail Stop 342, Memphis, Tennessee 38105, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Ohio State University College of Medicine, Columbus, Ohio 43205, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Wheeler
authors.affiliation: Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Ohio State University College of Medicine, Columbus, Ohio 43205, USA.
authors.forename: Oliver A
authors.initials: OA
authors.lastname: Hampton
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.|Departments of Pathology and Pediatrics, Ohio State University College of Medicine, 700 Children's Drive, Columbus, Ohio 43205, USA.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Gastier-Foster
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Ross
authors.affiliation: Cancer Therapy Evaluation Program, National Cancer Institute, 9609 Medical Center Drive, RM 5-W414, MSC 9737, Bethesda, Maryland 20892, USA.
authors.forename: Malcolm A
authors.initials: MA
authors.lastname: Smith
mesh_terms: D015331:Cohort Studies; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D009396:Wilms Tumor / Q000235:genetics* / Q000378:metabolism
chemical_list: D006657:Histones; C081448:MLLT1 protein, human; C489427:MYC protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors