Nature Communications (Dec 2023)
Genetic and epigenetic features of bilateral Wilms tumor predisposition in patients from the Children’s Oncology Group AREN18B5-Q
- 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
Affiliations
- Andrew J. Murphy
- Department of Surgery, St. Jude Children’s Research Hospital
- Changde Cheng
- Department of Computational Biology, St. Jude Children’s Research Hospital
- Justin Williams
- Department of Computational Biology, St. Jude Children’s Research Hospital
- Timothy I. Shaw
- Department of Computational Biology, St. Jude Children’s Research Hospital
- Emilia M. Pinto
- Department of Pathology, St. Jude Children’s Research Hospital
- Karissa Dieseldorff-Jones
- Department of Computational Biology, St. Jude Children’s Research Hospital
- Jack Brzezinski
- Department of Oncology, The Hospital for Sick Children
- Lindsay A. Renfro
- Children’s Oncology Group and Department of Population and Public Health Sciences, Keck School of Medicine of University of Southern California
- Brett Tornwall
- Children’s Oncology Group Statistics and Data Center
- Vicki Huff
- Department of Genetics, The University of Texas MD Anderson Cancer Center
- Andrew L. Hong
- Department of Pediatrics, Emory University School of Medicine
- Elizabeth A. Mullen
- Department of Pediatric Oncology, Dana-Farber/Boston Children’s Cancer and Blood Disorders Center and Harvard Medical School
- Brian Crompton
- Department of Pediatric Oncology, Dana-Farber/Boston Children’s Cancer and Blood Disorders Center and Harvard Medical School
- Jeffrey S. Dome
- Center for Cancer and Blood Disorders, Children’s National Hospital, Department of Pediatrics, George Washington University School of Medicine and Health Sciences
- Conrad V. Fernandez
- IWK Health Center and Dalhousie University
- James I. Geller
- Division of Oncology, Cincinnati Children’s Hospital Medical Center, University of Cincinnati
- Peter F. Ehrlich
- Section of Pediatric Surgery, C.S. Mott Children’s Hospital, University of Michigan
- Heather Mulder
- Department of Computational Biology, St. Jude Children’s Research Hospital
- Ninad Oak
- Department of Oncology, St. Jude Children’s Research Hospital
- Jamie Maciezsek
- Department of Pathology, St. Jude Children’s Research Hospital
- Carolyn M. Jablonowski
- Department of Surgery, St. Jude Children’s Research Hospital
- Andrew M. Fleming
- Department of Surgery, St. Jude Children’s Research Hospital
- Prahalathan Pichavaram
- Department of Surgery, St. Jude Children’s Research Hospital
- Christopher L. Morton
- Department of Surgery, St. Jude Children’s Research Hospital
- John Easton
- Department of Computational Biology, St. Jude Children’s Research Hospital
- Kim E. Nichols
- Department of Oncology, St. Jude Children’s Research Hospital
- Michael R. Clay
- Department of Pathology, University of Colorado Anschutz
- Teresa Santiago
- Department of Pathology, St. Jude Children’s Research Hospital
- Jinghui Zhang
- Department of Computational Biology, St. Jude Children’s Research Hospital
- Jun Yang
- Department of Surgery, St. Jude Children’s Research Hospital
- Gerard P. Zambetti
- Department of Pathology, St. Jude Children’s Research Hospital
- Zhaoming Wang
- Department of Computational Biology, St. Jude Children’s Research Hospital
- Andrew M. Davidoff
- Department of Surgery, St. Jude Children’s Research Hospital
- Xiang Chen
- Department of Computational Biology, St. Jude Children’s Research Hospital
- DOI
- https://doi.org/10.1038/s41467-023-43730-0
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 15
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.
