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

Samantha L Gadd, Vicki Huff, Amy Leanne Walz, Ariadne H.A.G. Ooms, Amy E. Armstrong, Daniela S. Gerhard, Malcolm A. Smith, Jaime M. Guidry Auvil, Daoud Meerzaman, Qing Rong Chen, Chih Hao Hsu, Chunhua Yan, Cu Nguyen, Ying Hu, Leandro C. Hermida, Tanja Davidsen, Patee Gesuwan, Yussanne Ma, Zusheng Zong, Andrew J. Mungall & 11 others Richard A. Moore, Marco A. Marra, Jeffrey S. Dome, Charles G. Mullighan, Jing Ma, David A. Wheeler, Oliver A. Hampton, Nicole Ross, Julie M. Gastier-Foster, Stefan T. Arold, Elizabeth J Perlman*

*Corresponding author for this work

Research output: Contribution to journalArticle

41 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1487-1494
Number of pages8
JournalNature Genetics
Volume49
Issue number10
DOIs
StatePublished - Oct 1 2017

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Wilms Tumor
DNA Copy Number Variations
DNA Methylation
MicroRNAs
Genes
Genome
Messenger RNA
Mutation
DNA

ASJC Scopus subject areas

  • Genetics

Cite this

Gadd, Samantha L ; Huff, Vicki ; Walz, Amy Leanne ; Ooms, Ariadne H.A.G. ; Armstrong, Amy E. ; Gerhard, Daniela S. ; Smith, Malcolm A. ; Guidry Auvil, Jaime M. ; 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. ; Moore, Richard A. ; Marra, Marco A. ; Dome, Jeffrey S. ; Mullighan, Charles G. ; Ma, Jing ; Wheeler, David A. ; Hampton, Oliver A. ; Ross, Nicole ; Gastier-Foster, Julie M. ; Arold, Stefan T. ; Perlman, Elizabeth J. / A Children's Oncology Group and TARGET initiative exploring the genetic landscape of Wilms tumor. In: Nature Genetics. 2017 ; Vol. 49, No. 10. pp. 1487-1494.
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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.",
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Gadd, SL, Huff, V, Walz, AL, Ooms, AHAG, Armstrong, AE, Gerhard, DS, Smith, MA, Guidry Auvil, JM, Meerzaman, D, Chen, QR, Hsu, CH, Yan, C, Nguyen, C, Hu, Y, Hermida, LC, Davidsen, T, Gesuwan, P, Ma, Y, Zong, Z, Mungall, AJ, Moore, RA, Marra, MA, Dome, JS, Mullighan, CG, Ma, J, Wheeler, DA, Hampton, OA, Ross, N, Gastier-Foster, JM, Arold, ST & Perlman, EJ 2017, 'A Children's Oncology Group and TARGET initiative exploring the genetic landscape of Wilms tumor', Nature Genetics, vol. 49, no. 10, pp. 1487-1494. https://doi.org/10.1038/ng.3940

A Children's Oncology Group and TARGET initiative exploring the genetic landscape of Wilms tumor. / Gadd, Samantha L; Huff, Vicki; Walz, Amy Leanne; Ooms, Ariadne H.A.G.; Armstrong, Amy E.; Gerhard, Daniela S.; Smith, Malcolm A.; Guidry Auvil, Jaime M.; 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.; Moore, Richard A.; Marra, Marco A.; Dome, Jeffrey S.; Mullighan, Charles G.; Ma, Jing; Wheeler, David A.; Hampton, Oliver A.; Ross, Nicole; Gastier-Foster, Julie M.; Arold, Stefan T.; Perlman, Elizabeth J.

In: Nature Genetics, Vol. 49, No. 10, 01.10.2017, p. 1487-1494.

Research output: Contribution to journalArticle

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AU - Gadd, Samantha L

AU - Huff, Vicki

AU - Walz, Amy Leanne

AU - Ooms, Ariadne H.A.G.

AU - Armstrong, Amy E.

AU - Gerhard, Daniela S.

AU - Smith, Malcolm A.

AU - Guidry Auvil, Jaime M.

AU - Meerzaman, Daoud

AU - Chen, Qing Rong

AU - Hsu, Chih Hao

AU - Yan, Chunhua

AU - Nguyen, Cu

AU - Hu, Ying

AU - Hermida, Leandro C.

AU - Davidsen, Tanja

AU - Gesuwan, Patee

AU - Ma, Yussanne

AU - Zong, Zusheng

AU - Mungall, Andrew J.

AU - Moore, Richard A.

AU - Marra, Marco A.

AU - Dome, Jeffrey S.

AU - Mullighan, Charles G.

AU - Ma, Jing

AU - Wheeler, David A.

AU - Hampton, Oliver A.

AU - Ross, Nicole

AU - Gastier-Foster, Julie M.

AU - Arold, Stefan T.

AU - Perlman, Elizabeth J

PY - 2017/10/1

Y1 - 2017/10/1

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