Genetic and epigenetic features of bilateral Wilms tumor predisposition in patients from the Children’s Oncology Group AREN18B5-Q

Bibliographic Details
Title: Genetic and epigenetic features of bilateral Wilms tumor predisposition in patients from the Children’s Oncology Group AREN18B5-Q
Authors: Andrew J. Murphy, Changde Cheng, Justin Williams, Timothy I. Shaw, Emilia M. Pinto, Karissa Dieseldorff-Jones, Jack Brzezinski, Lindsay A. Renfro, Brett Tornwall, Vicki Huff, Andrew L. Hong, Elizabeth A. Mullen, Brian Crompton, Jeffrey S. Dome, Conrad V. Fernandez, James I. Geller, Peter F. Ehrlich, Heather Mulder, Ninad Oak, Jamie Maciezsek, Carolyn M. Jablonowski, Andrew M. Fleming, Prahalathan Pichavaram, Christopher L. Morton, John Easton, Kim E. Nichols, Michael R. Clay, Teresa Santiago, Jinghui Zhang, Jun Yang, Gerard P. Zambetti, Zhaoming Wang, Andrew M. Davidoff, Xiang Chen
Source: Nature Communications, Vol 14, Iss 1, Pp 1-15 (2023)
Publisher Information: Nature Portfolio, 2023.
Publication Year: 2023
Collection: LCC:Science
Subject Terms: Science
More Details: Abstract Developing synchronous bilateral Wilms tumor suggests an underlying (epi)genetic predisposition. Here, we evaluate this predisposition in 68 patients using whole exome or genome sequencing (n = 85 tumors from 61 patients with matched germline blood DNA), RNA-seq (n = 99 tumors), and DNA methylation analysis (n = 61 peripheral blood, n = 29 non-diseased kidney, n = 99 tumors). We determine the predominant events for bilateral Wilms tumor predisposition: 1)pre-zygotic germline genetic variants readily detectable in blood DNA [WT1 (14.8%), NYNRIN (6.6%), TRIM28 (5%), and BRCA-related genes (5%)] or 2)post-zygotic epigenetic hypermethylation at 11p15.5 H19/ICR1 that may require analysis of multiple tissue types for diagnosis. Of 99 total tumor specimens, 16 (16.1%) have 11p15.5 normal retention of imprinting, 25 (25.2%) have 11p15.5 copy neutral loss of heterozygosity, and 58 (58.6%) have 11p15.5 H19/ICR1 epigenetic hypermethylation (loss of imprinting). Here, we ascertain the epigenetic and genetic modes of bilateral Wilms tumor predisposition.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2041-1723
Relation: https://doaj.org/toc/2041-1723
DOI: 10.1038/s41467-023-43730-0
Access URL: https://doaj.org/article/946f460fad5e41959f9465bb4f236137
Accession Number: edsdoj.946f460fad5e41959f9465bb4f236137
Database: Directory of Open Access Journals
More Details
ISSN:20411723
DOI:10.1038/s41467-023-43730-0
Published in:Nature Communications
Language:English