SALT LAKE CITY — In an effort to evaluate factors that could affect the likelihood of identifying a clinically actionable germline pathogenic variant (PV), a new study investigated a real-world multicenter cohort of patients with urinary tract cancer (UTC).
The University of Utah Huntsman Cancer Institute-led study, which included participations from VAMCs in Salt Lake City and Durham, NC, focused on primary disease sites including the bladder, urethra and upper tract. Patients were enrolled for research molecular testing of their germline and tumor.1
For the study published in JCO Precision Oncology, patients with UTC were identified from 10 cancer institutes of the Oncology Research Information Exchange Network consortium. Comparative analysis of the data set, which included abstracted clinical data with germline and tumor genomic data, was conducted.
Results indicated that 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),” according to the researchers. “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).”
The study noted that, 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.
“Tissue-based assessment of genomic instability, such as MSI, does not reliably indicate germline PV,” the authors pointed out. “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.”
- Kohlmann W, Nix DA, Pauley K, Greenberg S, et. Al. Inherited Germline Variants in Urinary Tract Cancer: A Multicenter Whole-Exome Sequencing Analysis and Correlation With Clinical Features and Tumor Genomics. JCO Precis Oncol. 2024 Jun;8:e2300697. doi: 10.1200/PO.23.00697. PMID: 38976819.
