Journal Article

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

Walz, Amy L, Zong, Zusheng, Hu, Ying, Armstrong, Amy E, Moore, Richard A, Gastier-Foster, Julie M, Nguyen, Cu, Chen, Qing-Rong, Marra, Marco A, Mungall, Andrew J, Hermida, Leandro C, Hampton, Oliver A, Meerzaman, Daoud, Wheeler, David A, Arold, Stefan T, Hsu, Chih Hao, Davidsen, Tanja, Yan, Chunhua, Perlman, Elizabeth J, Ross, Nicole, Dome, Jeffrey S, Ma, Yussanne, Ma, Jing, Gerhard, Daniela S, Smith, Malcolm A, Huff, Vicki, Gadd, Samantha, Guidry Auvil, Jaime M., Gesuwan, Patee, Ooms, Ariadne H A G, Mullighan, Charles G

2017

Overview

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.

• Publisher: Springer New York,Nature Publishing Group
• Subject: 38 / 38/23 / 38/39 / 38/91 / 45 / 631/67/1678 / 692/699/1585/1588/1683 / 82 / Agriculture / Amplification / Aneuploidy / Animal Genetics and Genomics / Bioinformatics / Biomedicine / Cancer / Cancer Research / Children / Copy number / Copy number variations / Deoxyribonucleic acid / Development and progression / DNA / DNA Methylation / DNA sequencing / Epigenesis, Genetic / Gain / Gene Dosage / Gene expression / Gene Expression Regulation, Neoplastic / Gene Function / Genes / Genes, Neoplasm / Genetic aspects / Genome-Wide Association Study / Genomes / Genomics / Germ-Line Mutation / Health aspects / Human Genetics / Humans / Insects / Kidney Neoplasms - genetics / MicroRNAs - biosynthesis / MicroRNAs - genetics / miRNA / mRNA / Mutation / Nephroblastoma / Oncogenes / p53 Protein / Protein Conformation / RNA, Messenger - biosynthesis / RNA, Messenger - genetics / RNA, Neoplasm - biosynthesis / RNA, Neoplasm - genetics / SIX gene family / Studies / Tumors / Wilms Tumor - genetics