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Updated: Jun 21, 2025
07:58
Cell-Free DNA Integrity Analysis in Urine Samples
Published on: January 5, 2017
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Inherited Germline Variants in Urinary Tract Cancer: A Multicenter Whole-Exome Sequencing Analysis and Correlation
Wendy Kohlmann1,2, David A Nix1, Kristen Pauley1
1University of Utah Huntsman Cancer Institute, Salt Lake City, UT.
JCO Precision Oncology
|July 8, 2024
Summary
Germline pathogenic variants (PVs) were found in 4.5% of urinary tract cancer patients. Non-bladder cancers, like upper tract and urethra, showed a higher PV prevalence, suggesting comprehensive germline testing is crucial.
Area of Science:
- Oncology
- Genetics
- Genomics
Background:
- Urinary tract cancer (UTC) encompasses various primary sites, including bladder, urethra, and upper tract.
- Molecular testing of germline and tumor DNA is increasingly utilized in cancer research.
- Identifying germline pathogenic variants (PVs) can inform treatment and hereditary cancer risk.
Purpose of the Study:
- To investigate a real-world cohort of UTC patients undergoing molecular testing.
- To evaluate factors influencing the detection of clinically actionable germline PVs.
- To assess the utility of genomic instability markers in predicting germline PVs.
Main Methods:
- A multicenter cohort of 354 UTC patients was analyzed.
- Germline and tumor genomic data were collected and compared.
- Prevalence of germline PVs was assessed across different primary disease sites.
Main Results:
- Clinically actionable germline PVs were identified in 4.5% (16/354) of patients.
- Patients with upper tract or urethra UTC had a higher PV prevalence (11%) compared to bladder UTC (3.6%).
- Genomic instability markers (MSI, LOH, etc.) did not reliably predict germline PVs.
Conclusions:
- Tissue-based genomic instability markers like MSI are not reliable indicators of germline PVs.
- Comprehensive germline testing, including homologous recombination repair (HRR) and mismatch repair (MMR) genes, is recommended.
- Approximately 1 in 10 patients with non-bladder UTC may harbor a detectable germline PV.
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