Samantha Gadd 1 , Vicki Huff 2 , Amy L. Walz 3 , Ariadne H.A.G. Ooms 1 , 4 , Amy E. Armstrong 3 , Daniela S. Gerhard 5 , Malcolm A. Smith 6 , Jaime M. Guidry Auvil 5 , Daoud Meerzaman 7 , Qing-Rong Chen 7 , Chih Hao Hsu 7 , Chunhua Yan 7 , Cu Nguyen 7 , Ying Hu 7 , Leandro C. Hermida 5 , Tanja Davidsen 7 , Patee Gesuwan 5 , Yussanne Ma 8 , Zusheng Zong 8 , Andrew J. Mungall 8 , Richard A. Moore 8 , Marco A. Marra 8 , 9 , Jeffrey S. Dome 10 , Charles G. Mullighan 11 , Jing Ma 11 , David A. Wheeler 12 , Oliver A. Hampton 12 , Nicole Ross 13 , Julie M. Gastier-Foster 13 , Stefan T. Arold 14 , Elizabeth J. Perlman 1
21 August 2017
Genome-wide sequencing, mRNA and miRNA expression, DNA copy number and methylation analyses were performed on 117 Wilms tumors, followed by targeted sequencing of 651 Wilms tumors. In addition to genes previously implicated in Wilms tumors ( WT1, CTNNB1, FAM123B, DROSHA, DGCR8, XPO5, DICER1, SIX1, SIX2, MLLT1, MYCN, and TP53), mutations were identified 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 let-7a 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.