Journal article
Inherited Germline Variants in Urinary Tract Cancer: A Multicenter Whole-Exome Sequencing Analysis and Correlation With Clinical Features and Tumor Genomics
JCO precision oncology, Vol.8(8), e2300697
06/2024
DOI: 10.1200/PO.23.00697
PMCID: PMC11813167
PMID: 38976819
Abstract
PURPOSE This study investigates a real-world multicenter cohort of patients with urinary tract cancer (UTC), with primary disease sites including the bladder, urethra, and upper tract, who enrolled for research molecular testing of their germline and tumor. The purpose of this study was to evaluate factors that could affect the likelihood of identifying a clinically actionable germline pathogenic variant (PV). METHODS Patients with UTC were identified from 10 cancer institutes of the Oncology Research Information Exchange Network consortium. The data set comprised abstracted clinical data with germline and tumor genomic data, and comparative analyses were conducted. RESULTS Clinically actionable germline PVs in cancer predisposition genes were identified in 16 (4.5%) of 354 patients. A higher proportion of patients with the urethra and the upper tract as the primary sites of disease had PVs with a prevalence of 11% (5/45), compared with only 3.6% (11/308) in those with the bladder as the primary site of disease ( P = .04). There were no significant differences in markers of genomic instability (such as tumor mutational burden, microsatellite instability [MSI], and loss of heterozygosity, copy number, and chromosomal instability) between those with PVs and those without ( P > .05). Of the PVs identified, 10 (62%) were in homologous recombination repair (HRR) genes, three (19%) in mismatch repair (MMR) genes, and three (19%) in genes associated with other pathways. CONCLUSION Tissue-based assessment of genomic instability, such as MSI, does not reliably indicate germline PV. A comprehensive clinical germline testing approach that includes HRR genes in addition to MMR genes is likely to yield PVs in approximately one of 10 patients with nonbladder primary disease sites such as the upper tract and the urethra.
Consider comprehensive germline multigene panel testing for upper urinary and urethra primary cancers.
Details
- Title: Subtitle
- Inherited Germline Variants in Urinary Tract Cancer: A Multicenter Whole-Exome Sequencing Analysis and Correlation With Clinical Features and Tumor Genomics
- Creators
- Wendy Kohlmann - University of UtahDavid A. Nix - Huntsman Cancer InstituteKristen Pauley - Huntsman Cancer InstituteSamantha Greenberg - University of UtahAaron Atkinson - University of UtahKenneth M. Boucher - University of UtahJill Kolesar - University of KentuckyEric A. Singer - The Ohio State UniversityStephen B. Edge - Roswell Park Comprehensive Cancer CenterMichelle L. ChurchmanLaura Graham - University of Colorado Cancer CenterBodour Salhia - University of Southern CaliforniaAlejandro Sanchez - University of UtahYousef Zakharia - University of IowaKenneth G. Nepple - University of IowaBryan P. Schneider - University of IowaLindsey Byrne - The Ohio State UniversityRohit K. Jain - Moffitt Cancer CenterJad Chahoud - Moffitt Cancer CenterSumati Gupta - University of UtahBing-Jian Feng - Lappeenranta-Lahti University of Technology
- Resource Type
- Journal article
- Publication Details
- JCO precision oncology, Vol.8(8), e2300697
- DOI
- 10.1200/PO.23.00697
- PMID
- 38976819
- PMCID
- PMC11813167
- NLM abbreviation
- JCO Precis Oncol
- ISSN
- 2473-4284
- eISSN
- 2473-4284
- Publisher
- LIPPINCOTT WILLIAMS & WILKINS
- Grant note
- US Department of Veterans Affairs Merit Review: 1T01 BX005765 National Cancer Institute of the National Institutes of Health: P30CA042014
The research reported in this article was supported in part by the US Department of Veterans Affairs Merit Review Award 1T01 BX005765 (to S.G.). The research reported in this publication used the Genetic Counseling, Cancer Biostatistics, and High Throughput Genomics and Cancer Bioinformatics at Huntsman Cancer Institute at the University of Utah and was supported by the National Cancer Institute of the National Institutes of Health under Award Number P30CA042014.
- Language
- English
- Date published
- 06/2024
- Academic Unit
- Pharmacy; Hematology, Oncology, and Blood & Marrow Transplantation; Pharmaceutical Sciences and Experimental Therapeutics; Urology; Internal Medicine
- Record Identifier
- 9984656630102771
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