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

sequencing reveals mutations across genome
Gadd S, Huff V, Walz AL, Ooms AHAG, Armstrong AE, Gerhard DS, Smith MA, Auvil JMG, 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.

Nature Genetics

August 21, 2017

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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Last updated: August 25, 2017