Posted: Tuesday, April 18, 2023
The use of a cell-free DNA assay to effectively establish a genome profile may be a suitable alternative approach for patients with urothelial carcinoma, according to a poster presentation given at the American Association for Cancer Research (AACR) Annual Meeting 2023 (Abstract 235/25). This assay may identify genomic mutations, classify urothelial carcinoma cases by molecular subtypes, and predict immune checkpoint molecular expression, explained Yuki Kita, PhD, of Kyoto University, Japan, and colleagues.
“Further investigation is needed as a promising minimally invasive assay to predict an immunotherapy responsiveness against metastatic urothelial carcinoma,” the study authors suggested.
A total of 48 patients with urothelial carcinoma were recruited for the study. All patients were treatment-naive. Blood and matched tissue samples were obtained from all patients and subjected to genomic profiling. If mutations were identified in a patient’s sample, they were filtered against matched leukocyte DNA. Samples also underwent RNA sequencing, immunohistochemistry, and polymerase chain reaction (PCR).
The study findings revealed 55 somatic mutations present in 22 of the collected cell-free DNA samples (45.8%). Of the identified somatic mutations, 47.3% were concurrently present in tumor tissues (n = 26). A total of 14 mutations were randomly selected to assess the efficacy of the variant allele frequency detected by digital PCR compared with next-generation sequencing, which was found to be significantly consistent between assays, the study authors reported. Moreover, circulating tumor DNA (ctDNA) fractions greater than 2% of the total cell-free DNA sample were identified in 6 of the 22 collected samples. This elevated ctDNA seems to be associated with the basal molecular subtype (P < .01), an advanced clinical tumor stage (P = .04), and increased PD-L 1 expression on immunohistochemistry (P = .02).
Disclosure: The study authors reported no conflicts of interest.