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

2017; Nature Portfolio; Volume: 49; Issue: 10 Linguagem: Inglês

10.1038/ng.3940

1546-1718

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 M. 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 Hampton, Nicole Ross, Julie M. Gastier‐Foster, Stefan T. Arold, Elizabeth J. Perlman,

Renal and related cancers

Elizabeth Perlman and colleagues use genome-wide sequencing, RNA expression, DNA copy number and methylation analyses to characterize the genomic landscape of Wilms tumors. Their integrated analyses implicate two major classes of genetic changes in Wilms tumors that preserve the progenitor state and/or interrupt normal kidney development. 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.