학술논문
Genetic and epigenetic features of bilateral Wilms tumor predisposition in patients from the Children’s Oncology Group AREN18B5-Q
Document Type
article
Author
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)
Subject
Language
English
ISSN
2041-1723
Abstract
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.