TY - JOUR
T1 - A Children's Oncology Group and TARGET initiative exploring the genetic landscape of Wilms tumor
AU - Gadd, Samantha
AU - Huff, Vicki
AU - Walz, Amy L.
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.
N1 - Publisher Copyright:
© 2017 Nature America, Inc., part of Springer Nature. All rights reserved.
PY - 2017/10/1
Y1 - 2017/10/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85030164667&partnerID=8YFLogxK
U2 - 10.1038/ng.3940
DO - 10.1038/ng.3940
M3 - Article
C2 - 28825729
AN - SCOPUS:85030164667
SN - 1061-4036
VL - 49
SP - 1487
EP - 1494
JO - Nature Genetics
JF - Nature Genetics
IS - 10
ER -