@article{10909141e8fe4a25b17a3f72bb7dadc6,
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.",
author = "Perlman, {Elizabeth J.} and Samantha Gadd and Arold, {Stefan T.} and Anand Radhakrishnan and Gerhard, {Daniela S.} and Lawrence Jennings and Vicki Huff and Auvil, {Jaime M.Guidry} and Davidsen, {Tanja M.} and Dome, {Jeffrey S.} and Daoud Meerzaman and Hsu, {Chih Hao} and Cu Nguyen and James Anderson and Yussanne Ma and Mungall, {Andrew J.} and Moore, {Richard A.} and Marra, {Marco A.} and Mullighan, {Charles G.} and Jing Ma and Wheeler, {David A.} and Hampton, {Oliver A.} and Gastier-Foster, {Julie M.} and Nicole Ross and Smith, {Malcolm A.}",
note = "Funding Information: The TARGET initiative is supported by NCI Grant U10 CA98543. Work performed under contracts from the National Cancer Institute, US National Institutes of Health within HHSN261200800001E include specimen processing (the Children{\textquoteright}s Oncology Group Biopathology Center (BPC), whole genomic sequencing (Complete Genomics, Inc), whole exomic sequencing (Baylor College of Medicine) and specific capture followed by sequencing (British Columbia Cancer Agency Genome Sciences Centre). The content of this publication does not necessarily reflect the views of policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. The authors thank Patee Gesuwan and Leandro Hermida and the Data Coordinating Center for their support. We thank Karen Carty and Franceline Huser and for help and assistance with the recombinant protein production and DSF analysis. We thank the KAUST bioscience core lab for access to the MicroCal ITC200 microcalorimeter. We also thank the Clinical Applications of Core Technology Laboratory of the Hartwell Center for Bioinformatics and Biotechnology of St Jude Children{\textquoteright}s Research Hospital for performing the copy number analysis. The authors are grateful for the project management expertize of Karen Novik and Laura Monovich, and for the technical expertize of Patricia Beezhold, Donna Kersey, Debbie-Payne Turner, Mary McNulty and Yvonne Moyer. This work would not be possible without the dedication of all the experts within the many disciplines both at the local institutions and centrally within the Children{\textquoteright}s Oncology Group. They enable the coordination and accurate annotation required for the therapeutic and biology protocols that form the basis for the TARGET studies. Financial Support: NCI U10 CA98543 (E.J.P., J.M.G.-F. and M.A.M.); NIH U10CA42326 (E.J.P.); U10CA98543 (J.S.D. and E.J.P.); U24 CA114766; UO1CA88131 (E.J.P.), the IDP Foundation (E.J.P.), the American and Lebanese Syrian Associated Charities of St Jude (J.M. and C.M.) and the King Abdullah University of Science and Technology (S.T.A. and A.R.).",
year = "2015",
month = dec,
day = "4",
doi = "10.1038/ncomms10013",
language = "English (US)",
volume = "6",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}