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Updated: Aug 13, 2025
Cell-Free DNA Integrity Analysis in Urine Samples
Published on: January 5, 2017
Clinical sequencing identifies potential actionable alterations in a high rate of urachal and primary bladder
Melinda Varadi1, Nikolett Nagy1, Henning Reis2,3
1Department of Urology, Semmelweis University, Budapest, Hungary.
Objective:
Administration of targeted therapies provides a promising treatment strategy for urachal adenocarcinoma (UrC) or primary bladder adenocarcinoma (PBAC); however, the selection of appropriate drugs remains difficult. Here, we aimed to establish a routine compatible methodological pipeline for the identification of the most important therapeutic targets and potentially effective drugs for UrC and PBAC.
Methods:
Next-generation sequencing, using a 161 cancer driver gene panel, was performed on 41 UrC and 13 PBAC samples. Clinically relevant alterations were filtered, and therapeutic interpretation was performed by in silico evaluation of drug-gene interactions.
Results:
After data processing, 45/54 samples passed the quality control. Sequencing analysis revealed 191 pathogenic mutations in 68 genes. The most frequent gain-of-function mutations in UrC were found in KRAS (33%), and MYC (15%), while in PBAC KRAS (25%), MYC (25%), FLT3 (17%) and TERT (17%) were recurrently affected. The most frequently affected pathways were the cell cycle regulation, and the DNA damage control pathway. Actionable mutations with at least one available approved drug were identified in 31/33 (94%) UrC and 8/12 (67%) PBAC patients.
Conclusions:
In this study, we developed a data-processing pipeline for the detection and therapeutic interpretation of genetic alterations in two rare cancers. Our analyses revealed actionable mutations in a high rate of cases, suggesting that this approach is a potentially feasible strategy for both UrC and PBAC treatments.
Insights
A new method identifies actionable mutations for urachal adenocarcinoma (UrC) and primary bladder adenocarcinoma (PBAC). This pipeline aids in selecting targeted therapies for these rare cancers, improving treatment selection.
Area of Science:
- Oncology
- Genomics
- Translational Medicine
Background:
- Targeted therapies offer promise for urachal adenocarcinoma (UrC) and primary bladder adenocarcinoma (PBAC).
- Selecting effective drugs for these rare cancers is challenging.
- Identifying key therapeutic targets is crucial for treatment optimization.
Purpose of the Study:
- To establish a reproducible methodological pipeline for identifying therapeutic targets and drugs for UrC and PBAC.
- To analyze genetic alterations in UrC and PBAC to guide treatment decisions.
Main Methods:
- Next-generation sequencing of 161 cancer driver genes in 41 UrC and 13 PBAC samples.
- Filtering clinically relevant alterations and performing in silico drug-gene interaction evaluation.
- Developing a data-processing pipeline for genetic alteration detection and therapeutic interpretation.
Main Results:
- Sequencing identified 191 pathogenic mutations in 68 genes across 45/54 samples.
- Frequent mutations included KRAS, MYC, FLT3, and TERT, affecting cell cycle and DNA damage pathways.
- Actionable mutations with available drugs were found in 94% of UrC and 67% of PBAC patients.
Conclusions:
- A data-processing pipeline was developed for genetic alteration analysis in rare cancers.
- Actionable mutations were identified in a high proportion of UrC and PBAC cases.
- This approach shows feasibility for guiding targeted therapy selection in UrC and PBAC.
