Genetic changes associated with relapse in favorable histology Wilms tumor: A Children’s Oncology Group AREN03B2 study
Year: 2022
Type: article
Abstract: Over the last decade, sequencing of primary tumors has clarified the genetic underpinnings of Wilms tumor but has not affected therapy, outcome, or toxicity. We now sharpen our focus on relapse samples from the umbrella AREN03B2 study. We show that over 40% of relapse samples contain mutations in SIX1 or genes of the MYCN network, drivers of progenitor proliferation. Not previously seen in large studies of primary Wilms tumors, DIS3 and TERT are now identified as recurrently mutated. The analysis of primary-relapse tumor pairs suggests that 11p15 loss of heterozygosity (and other copy number changes) and mutations in WT1 and MLLT1 typically occur early, but mutations in SIX1, MYCN, and WTX are late developments in some individuals. Most strikingly, 75% of relapse samples had gain of 1q, providing strong conceptual support for studying circulating tumor DNA in clinical trials to better detect 1q gain earlier and monitor response.
Source: Cell Reports Medicine
Institutions: Northwestern University, Lurie Children's Hospital, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, The University of Texas MD Anderson Cancer Center, University of Southern California, Dalhousie University, Izaak Walton Killam Health Centre, Harvard University, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, University of North Carolina at Chapel Hill, UNC Lineberger Comprehensive Cancer Center, Nationwide Children's Hospital, The Ohio State University, Frederick National Laboratory for Cancer Research
Language: English
Topic: Renal and related cancers
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,200
Funders: U.S. Department of Health and Human Services, St. Baldrick's Foundation, Harvard University, Broad Institute, Government of South Australia, National Institutes of Health, National Cancer Institute, National Institute of Environmental Health Sciences, Moonshot Research and Development Program, Cancer Moonshot
Awards: Children's Oncology Group Statistics and Data Center Grant, Support for Human Specimen Banking in NCI-Sponsored Clinical Trials-(CGB), Children's Oncology Group Statistics and Data Center, G5060448047, COG NCTN Network Group Operations Center, G5975062161, G6012682559, Children's Oncology Group Chair's Grant, G8422249695, UNC Center for Environmental Health and Susceptibility, COG Biospecimen Bank to Support NCI NCTN (U24)
OpenAlex ID: W4281567617