You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology II1 Apr 2016MP61-17 ASSOCIATIONS OF PROGRESSION IN T1G3 BLADDER CANCERS AND MUTATION HETEROGENEITY IN 20 CANCER-RELATED GENES Karsten Salomo, Doreen Huebner, Jana Hahm, Joern Meinel, Vladimir Novotny, Manja Boehme, Susanne Fuessel, and Manfred P. Wirth Karsten SalomoKarsten Salomo More articles by this author , Doreen HuebnerDoreen Huebner More articles by this author , Jana HahmJana Hahm More articles by this author , Joern MeinelJoern Meinel More articles by this author , Vladimir NovotnyVladimir Novotny More articles by this author , Manja BoehmeManja Boehme More articles by this author , Susanne FuesselSusanne Fuessel More articles by this author , and Manfred P. WirthManfred P. Wirth More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.891AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES With about 70-80% non-muscle-invasive bladder cancers (NMIBC) are by far the most common urothelial carcinomas at the time of diagnosis. NMIBC are characterized by a high level of clinical and pathological heterogeneity. Especially high grade NMIBC of stage T1 are prone to progress to an aggressive disease. Therefore, biomarkers to differentiate the progression risk in T1G3 bladder cancers would be greatly beneficial. As muscle-invasive bladder cancers (MIBC) are characterized by mutations, e.g. in TP53 and RB1, which differ from mutations in NMIBC, e.g. in FGFR3 and RAS, a set of mutations might exist to better stratify the risk of progression in T1G3 tumors. METHODS We assessed the mutation status of 20 bladder cancer-associated genes in tumor and corresponding tumor-free formalin-fixed paraffin-embedded (FFPE) bladder tissues (23x <T1G3, 43x T1G3 without progress, 30x T1G3 with progress, 24x MIBC) as well as 12 lymph DNAs applying Illumina TruSeq Custom Amplicon next-generation sequencing. In addition, multiplexed SNaPshot assays covering important, known mutations in FGFR3, PIK3CA and TERT promoter region were applied for FFPE- and urine samples. RESULTS In our analyses the CREBBP gene showed the highest number of mutations, while ARID1A mutations were discovered in most patients. In total, 482 reoccurring mutations, mostly abundant only in a small portion of the samples, could be discovered. Of the most frequent mutations, also analyzed with SNaPshot assays, the FGFR3 mutation S249C was found in 39% (<T1G3), 20% (T1G3) and 10% (MIBC) of the samples. The FGFR3 mutations R248C and G372C were only present in patients with <T1G3 and T1G3 without progress. About 75% of patients showed one of the two mutually exclusive TERT promoter mutations at positions -124bp and -146bp independent from tumor stage and progress. Of the PIK3CA mutations, E545K was the most frequent one (6-17%). CONCLUSIONS Mutation heterogeneity and a particular set of mutations seem to be related to the risk of progression in T1G3 bladder cancers. Preliminary results show that on average 10% of all mutations found enriched in T1G3 bladder cancers are significantly related with tumor stage and grade, progression or recurrence. Furthermore, highly abundant mutations may be potential candidates for urine-based bladder cancer diagnosis. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e810 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Karsten Salomo More articles by this author Doreen Huebner More articles by this author Jana Hahm More articles by this author Joern Meinel More articles by this author Vladimir Novotny More articles by this author Manja Boehme More articles by this author Susanne Fuessel More articles by this author Manfred P. Wirth More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...