Raphael Brandao Moreira
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Matheus Bongers Alessandretti
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Aline Da Rocha Lino
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Rodnei Merlrina Martins Junior
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Marcus Paulo Fernandes Amarante
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315 Background: Metastatic PA is a lethal malignancy with poor prognosis and limited therapeutic options. We hypothesized that a comprehensive next-generation sequencing (NGS) assay could identify novel therapy targets not routinely explored in PA patients. Methods: We included patients with advanced pancreatic adenocarcinoma (PA) with accessible lesion for biopsy. Paraffin-embedded tumor tissues were evaluated by the method of NGS (Foundation Medicine, Cambridge, MA, USA). Hybridization capture of 3,769 exons from 236 cancer-related genes and 47 introns of 19 genes commonly rearranged in cancer was applied to ≥ 50 ng of DNA extracted from 10 PA specimens and sequenced to high, uniform coverage. Genomic alterations (GAs), were characterized and reported for each patient sample. Actionable GAs were defined as those identifying anti-cancer targeted therapies either available on the market or in registered clinical trials. Results: A total of 10 PA patients were included. Median age was 56 years (range 31-79). All cases harbored at least one GA with a mean of 2.7 actionable GAs per tumor. The most common actionable GAs were KRAS (90%), PTCH1 (20%), STK11 (10%) and GNAS (10%). KRAS mutations potentially treatable with MEK-inhibitor were identified in 9 patients. However, none of them received a MEK-inhibitor. Activating STK11 point mutations not detectable by IHC/FISH, potentially targetable with m-Tor inhibitor therapies were identified in 1 patient, who received everolimus and had a long-lasting (> 6 months) partial response. Conclusions: NGS of PA was able to reveal genomic alterations that may be potentially responsive to available targeted therapy. We are just at the dawn of exploring this strategy and NGS can effectively contribute for increasing the understanding of the disease.
Genome-Wide Characterization of Pancreatic Adenocarcinoma Patients Using Next Generation Sequencing
