Next-generation sequencing reveals potential predictive biomarkers and targets of therapy for urothelial carcinoma in situ of the urinary bladder.

Next-generation sequencing reveals potential predictive biomarkers and targets of therapy for urothelial carcinoma in situ of the urinary bladder. Am J Pathol. 2019 Nov 14;: Authors: Garczyk S, Ortiz-Brüchle N, Schneider U, Lurje I, Guricova K, Gaisa NT, Lorsy E, Lindemann-Docter K, Heidenreich A, Knüchel R Abstract Bacillus Calmette-Guérin instillation following removal of the tumor is the first-line of treatment for urothelial carcinoma in situ (CIS), the precursor lesion of most muscle-invasive bladder cancers. Bacillus Calmette-Guérin therapy fails in >50% of cases and second-line radical cystectomy is associated with overtreatment and drastic lifestyle consequences. Given the need for alternative bladder-preserving therapies, we identified genomic alterations (GAs) in urothelial CIS having the potential to predict response to targeted therapies. Laser-capture microdissection was applied to isolate 30 samples (25 CIS and five muscle controls) from 26 fresh-frozen cystectomy specimens. Targeted next-generation sequencing of 31 genes was performed. The panel comprised genes frequently affected in muscle-invasive bladder cancer of non-papillary origin, focusing on potentially actionable GAs described to predict response to approved targeted therapies or drugs that are in registered clinical trials. Ninety-two percent of CIS patients harbored at least one potentially actionable GA, which were were identified in TP53/cell cycle...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research