A Children's Oncology Group and TARGET initiative exploring the genetic landscape of Wilms tumor

Handle URI:
http://hdl.handle.net/10754/625743
Title:
A Children's Oncology Group and TARGET initiative exploring the genetic landscape of Wilms tumor
Authors:
Gadd, Samantha; Huff, Vicki; Walz, Amy L; Ooms, Ariadne H A G; Armstrong, Amy E; Gerhard, Daniela S; Smith, Malcolm A ( 0000-0001-9880-9876 ) ; Auvil, Jaime M Guidry; Meerzaman, Daoud; Chen, Qing-Rong; Hsu, Chih Hao; Yan, Chunhua; Nguyen, Cu; Hu, Ying; Hermida, Leandro C; Davidsen, Tanja; Gesuwan, Patee; Ma, Yussanne; Zong, Zusheng; Mungall, Andrew J ( 0000-0002-0905-2742 ) ; Moore, Richard A; Marra, Marco A; Dome, Jeffrey S; Mullighan, Charles G ( 0000-0002-1871-1850 ) ; Ma, Jing; Wheeler, David A; Hampton, Oliver A; Ross, Nicole; Gastier-Foster, Julie M; Arold, Stefan T. ( 0000-0001-5278-0668 ) ; Perlman, Elizabeth J ( 0000-0001-6853-6221 )
Abstract:
We performed genome-wide sequencing and analyzed mRNA and miRNA expression, DNA copy number, and DNA methylation in 117 Wilms tumors, followed by targeted sequencing of 651 Wilms tumors. In addition to genes previously implicated in Wilms tumors (WT1, CTNNB1, AMER1, DROSHA, DGCR8, XPO5, DICER1, SIX1, SIX2, MLLT1, MYCN, and TP53), we identified mutations in genes not previously recognized as recurrently involved in Wilms tumors, the most frequent being BCOR, BCORL1, NONO, MAX, COL6A3, ASXL1, MAP3K4, and ARID1A. DNA copy number changes resulted in recurrent 1q gain, MYCN amplification, LIN28B gain, and MIRLET7A loss. Unexpected germline variants involved PALB2 and CHEK2. Integrated analyses support two major classes of genetic changes that preserve the progenitor state and/or interrupt normal development.
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division; Computational Bioscience Research Center (CBRC)
Citation:
Gadd S, Huff V, Walz AL, Ooms AHAG, Armstrong AE, et al. (2017) A Children’s Oncology Group and TARGET initiative exploring the genetic landscape of Wilms tumor. Nature Genetics 49: 1487–1494. Available: http://dx.doi.org/10.1038/ng.3940.
Publisher:
Springer Nature
Journal:
Nature Genetics
Issue Date:
21-Aug-2017
DOI:
10.1038/ng.3940
Type:
Article
ISSN:
1061-4036; 1546-1718
Sponsors:
The authors thank the Clinical Applications of Core Technology Laboratory of the Hartwell Center for Bioinformatics and Biotechnology of St. Jude Children's Research Hospital for performing the copy number analysis, and the Northwestern University Genomic Core facility for performing the methylation analysis. The authors are grateful for the expertise of K. Novik, L. Monovich, P. Beezhold, D. Kersey, D. Turner, M. McNulty, and Y. Moyer. This work would not be possible without the dedication of the experts within the many clinical disciplines at local institutions and within the Children's Oncology Group and National Wilms Tumor Study Group, the patients, and their families. The TARGET initiative is supported by US National Cancer Institute (NCI) grant U10 CA98543. Work performed under contracts from the NCI within HHSN261200800001E includes specimen processing (the COG Biopathology Center), WGS (CGI, Inc.), whole-exome sequencing (Baylor College of Medicine), miRNA-seq, RNA-seq, and target capture sequencing (BCCA Genome Sciences Center). Financial support was provided by TARGET U10 CA98543 contract HHSN261200800001E and National Institutes of Health (NIH) grants U10CA180886, NIH U10CA180899, NIH U10CA098413, and NIH U10CA42326 (E.J.P.); U10CA98543 (J.S.D., E.J.P.); U24 CA114766 and UO1CA88131 (E.J.P.), and NCI T32 CA079447 (A.L.W., A.E.A.). This work is also supported by the American and Lebanese Syrian Associated Charities of St. Jude (J.M., C.G.M.), the King Abdullah University of Science and Technology (S.T.A.), and the Dutch Cancer Society (A.H.A.G.O.). The content of this publication does not necessarily reflect the views or policies of the US Department of Health and Human Services, nor does the mention of trade names, commercial products, or organizations imply endorsement by the US Government.
Additional Links:
https://www.nature.com/ng/journal/vaop/ncurrent/full/ng.3940.html
Appears in Collections:
Articles; Computational Bioscience Research Center (CBRC); Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorGadd, Samanthaen
dc.contributor.authorHuff, Vickien
dc.contributor.authorWalz, Amy Len
dc.contributor.authorOoms, Ariadne H A Gen
dc.contributor.authorArmstrong, Amy Een
dc.contributor.authorGerhard, Daniela Sen
dc.contributor.authorSmith, Malcolm Aen
dc.contributor.authorAuvil, Jaime M Guidryen
dc.contributor.authorMeerzaman, Daouden
dc.contributor.authorChen, Qing-Rongen
dc.contributor.authorHsu, Chih Haoen
dc.contributor.authorYan, Chunhuaen
dc.contributor.authorNguyen, Cuen
dc.contributor.authorHu, Yingen
dc.contributor.authorHermida, Leandro Cen
dc.contributor.authorDavidsen, Tanjaen
dc.contributor.authorGesuwan, Pateeen
dc.contributor.authorMa, Yussanneen
dc.contributor.authorZong, Zushengen
dc.contributor.authorMungall, Andrew Jen
dc.contributor.authorMoore, Richard Aen
dc.contributor.authorMarra, Marco Aen
dc.contributor.authorDome, Jeffrey Sen
dc.contributor.authorMullighan, Charles Gen
dc.contributor.authorMa, Jingen
dc.contributor.authorWheeler, David Aen
dc.contributor.authorHampton, Oliver Aen
dc.contributor.authorRoss, Nicoleen
dc.contributor.authorGastier-Foster, Julie Men
dc.contributor.authorArold, Stefan T.en
dc.contributor.authorPerlman, Elizabeth Jen
dc.date.accessioned2017-10-03T12:49:37Z-
dc.date.available2017-10-03T12:49:37Z-
dc.date.issued2017-08-21en
dc.identifier.citationGadd S, Huff V, Walz AL, Ooms AHAG, Armstrong AE, et al. (2017) A Children’s Oncology Group and TARGET initiative exploring the genetic landscape of Wilms tumor. Nature Genetics 49: 1487–1494. Available: http://dx.doi.org/10.1038/ng.3940.en
dc.identifier.issn1061-4036en
dc.identifier.issn1546-1718en
dc.identifier.doi10.1038/ng.3940en
dc.identifier.urihttp://hdl.handle.net/10754/625743-
dc.description.abstractWe performed genome-wide sequencing and analyzed mRNA and miRNA expression, DNA copy number, and DNA methylation in 117 Wilms tumors, followed by targeted sequencing of 651 Wilms tumors. In addition to genes previously implicated in Wilms tumors (WT1, CTNNB1, AMER1, DROSHA, DGCR8, XPO5, DICER1, SIX1, SIX2, MLLT1, MYCN, and TP53), we identified mutations in genes not previously recognized as recurrently involved in Wilms tumors, the most frequent being BCOR, BCORL1, NONO, MAX, COL6A3, ASXL1, MAP3K4, and ARID1A. DNA copy number changes resulted in recurrent 1q gain, MYCN amplification, LIN28B gain, and MIRLET7A loss. Unexpected germline variants involved PALB2 and CHEK2. Integrated analyses support two major classes of genetic changes that preserve the progenitor state and/or interrupt normal development.en
dc.description.sponsorshipThe authors thank the Clinical Applications of Core Technology Laboratory of the Hartwell Center for Bioinformatics and Biotechnology of St. Jude Children's Research Hospital for performing the copy number analysis, and the Northwestern University Genomic Core facility for performing the methylation analysis. The authors are grateful for the expertise of K. Novik, L. Monovich, P. Beezhold, D. Kersey, D. Turner, M. McNulty, and Y. Moyer. This work would not be possible without the dedication of the experts within the many clinical disciplines at local institutions and within the Children's Oncology Group and National Wilms Tumor Study Group, the patients, and their families. The TARGET initiative is supported by US National Cancer Institute (NCI) grant U10 CA98543. Work performed under contracts from the NCI within HHSN261200800001E includes specimen processing (the COG Biopathology Center), WGS (CGI, Inc.), whole-exome sequencing (Baylor College of Medicine), miRNA-seq, RNA-seq, and target capture sequencing (BCCA Genome Sciences Center). Financial support was provided by TARGET U10 CA98543 contract HHSN261200800001E and National Institutes of Health (NIH) grants U10CA180886, NIH U10CA180899, NIH U10CA098413, and NIH U10CA42326 (E.J.P.); U10CA98543 (J.S.D., E.J.P.); U24 CA114766 and UO1CA88131 (E.J.P.), and NCI T32 CA079447 (A.L.W., A.E.A.). This work is also supported by the American and Lebanese Syrian Associated Charities of St. Jude (J.M., C.G.M.), the King Abdullah University of Science and Technology (S.T.A.), and the Dutch Cancer Society (A.H.A.G.O.). The content of this publication does not necessarily reflect the views or policies of the US Department of Health and Human Services, nor does the mention of trade names, commercial products, or organizations imply endorsement by the US Government.en
dc.publisherSpringer Natureen
dc.relation.urlhttps://www.nature.com/ng/journal/vaop/ncurrent/full/ng.3940.htmlen
dc.titleA Children's Oncology Group and TARGET initiative exploring the genetic landscape of Wilms tumoren
dc.typeArticleen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.contributor.departmentComputational Bioscience Research Center (CBRC)en
dc.identifier.journalNature Geneticsen
dc.contributor.institutionDepartment of Pathology and Laboratory Medicine, Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine and Robert H. Lurie Cancer Center, Chicago, Illinois, USA.en
dc.contributor.institutionDepartment of Genetics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.en
dc.contributor.institutionDivision of Hematology-Oncology and Transplantation, Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.en
dc.contributor.institutionDepartment of Pathology, Princess Maxima Center for Pediatric Oncology, Utrecht, the Netherlands.en
dc.contributor.institutionOffice of Cancer Genomics, National Cancer Institute, Bethesda, Maryland, USA.en
dc.contributor.institutionCancer Therapy Evaluation Program, National Cancer Institute, Bethesda, Maryland, USA.en
dc.contributor.institutionCenter for Biomedical Informatics and Information Technology, National Cancer Institute, Bethesda, Maryland, USA.en
dc.contributor.institutionCanada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency (BCCA), Vancouver, British Columbia, Canada.en
dc.contributor.institutionDepartment of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.en
dc.contributor.institutionDivision of Pediatric Hematology/Oncology, Children's National Medical Center, Washington DC, USA.en
dc.contributor.institutionDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.en
dc.contributor.institutionDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.en
dc.contributor.institutionDepartment of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Ohio State University College of Medicine, Columbus, Ohio, USA.en
kaust.authorArold, Stefan T.en
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