Beitragstitel | Identifying DNA biomarkers of Bacillus Calmette-Guerin (BCG) resistance in non-muscle-invasive bladder cancer |
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Beitragscode | P053 |
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Präsentationsform | Freie Mitteilungen |
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Abstract-Text |
Introduction Failure to respond to Bacillus Calmette Guérin (BCG) therapy is associated with disease progression and worse outcome. Currently, patients who do not respond to BCG therapy are only identified by their adverse clinicopathological features such as tumour grade, stage, multiple tumours, and presence of CIS. For these patients we are in need of better prediction of the response to BCG. Here, we analysed matched pre- and post-BCG tumour samples of BCG non-responsive patients and compared these to the tumours of BCG responsive patients. Method Formalin-fixed, paraffin-embedded tissue sections were retrospectively obtained from a cohort of 60 BCG responsive patients and 32 BCG non-responsive patients treated at the University Hospital Basel. For the 32 non-responsive patients, 19 presented a recurrence and 13 a progression. We performed targeted DNA sequencing of 50 relevant bladder cancer genes on all samples. Results For BCG non-responsive patients, the mean time of recurrence or progression after BCG therapy was 23 +/- 13.9 (95 % CI) months. At the time of abstract writing, results of the DNA analysis of 20 patients were available, representing 12 relapsed and 8 BCG responsive patients. The most represented mutations were TERT (13/20) and TP53 (12/20). In BCG non-responders, FGFR3 and KMT2D mutations were enriched in the pre-BCG cohort as compared to the post-BCG cohort (21% vs. 0% and 32% vs. 8%) while TP53 mutations were enriched post-BCG (57% vs. 75%). So far, all analysed non-responsive patients showed an overlapping mutational pattern in the pre and post BCG tumour sample but 5/12 exhibited additional loss or gain of driver mutations. Conclusions The high similarity of mutational patterns in half of the pre- and post-BCG samples may suggest a potential inherent resistance to BCG therapy while in the other half of the patients new mutations developed that may have contributed to BCG resistance. DNA sequencing for the other 72 patients is currently being analysed and more results will be presented at the congress. |