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

Samantha Gadd; Vicki Huff; Amy L. 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; 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

doi:10.1038/ng.3940

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

Samantha Gadd, Vicki Huff, Amy L. 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. MungallRichard 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

Genetics

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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.

Original language	English (US)
Pages (from-to)	1487-1494
Number of pages	8
Journal	Nature Genetics
Volume	49
Issue number	10
DOIs	https://doi.org/10.1038/ng.3940
State	Published - Oct 1 2017

ASJC Scopus subject areas

Genetics

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Gadd, S., Huff, V., Walz, A. L., Ooms, A. H. A. G., Armstrong, A. E., Gerhard, D. S., Smith, M. A., Guidry Auvil, J. M., Meerzaman, D., Chen, Q. R., Hsu, C. H., Yan, C., Nguyen, C., Hu, Y., Hermida, L. C., Davidsen, T., Gesuwan, P., Ma, Y., Zong, Z., ... Perlman, E. J. (2017). A Children's Oncology Group and TARGET initiative exploring the genetic landscape of Wilms tumor. Nature Genetics, 49(10), 1487-1494. https://doi.org/10.1038/ng.3940

Gadd, S, 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

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

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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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.

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

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