Heining, Christoph; Horak, Peter; Uhrig, Sebastian; Codo, Paula L; Klink, Barbara; Hutter, Barbara; Fröhlich, Martina; Bonekamp, David; Richter, Daniela; Steiger, Katja; Penzel, Roland; Endris, Volker; Ehrenberg, Karl Roland; Frank, Stephanie; Kleinheinz, Kortine; Toprak, Umut H; Schlesner, Matthias; Mandal, Ranadip; Schulz, Lothar; Lambertz, Helmut; Fetscher, Sebastian; Bitzer, Michael; Malek, Nisar P; Horger, Marius; Giese, Nathalia A; Strobel, Oliver; Hackert, Thilo; Springfeld, Christoph; Feuerbach, Lars; Bergmann, Frank; Schröck, Evelin; von Kalle, Christof; Weichert, Wilko; Scholl, Claudia; Ball, Claudia R; Stenzinger, Albrecht; Brors, Benedikt; Fröhling, Stefan; Glimm, Hanno     «

Heining, Christoph; Horak, Peter; Uhrig, Sebastian; Codo, Paula L; Klink, Barbara; Hutter, Barbara; Fröhlich, Martina; Bonekamp, David; Richter, Daniela; Steiger, Katja; Penzel, Roland; Endris, Volker; Ehrenberg, Karl Roland; Frank, Stephanie; Kleinheinz, Kortine; Toprak, Umut H; Schlesner, Matthias; Mandal, Ranadip; Schulz, Lothar; Lambertz, Helmut; Fetscher, Sebastian; Bitzer, Michael; Malek, Nisar P; Horger, Marius; Giese, Nathalia A; Strobel, Oliver; Hackert, Thilo; Springfeld, Christoph; Fe...     »

We used whole-genome and transcriptome sequencing to identify clinically actionable genomic alterations in young adults with pancreatic ductal adenocarcinoma (PDAC). Molecular characterization of 17 patients with PDAC enrolled in a precision oncology program revealed gene fusions amenable to pharmacologic inhibition by small-molecule tyrosine kinase inhibitors in all patients with wild-type () tumors (4 of 17). These alterations included recurrent rearrangements predicted to drive PDAC development through aberrant ERBB receptor-mediated signaling, and pharmacologic ERBB inhibition resulted in clinical improvement and remission of liver metastases in 2 patients with -rearranged tumors that had proved resistant to standard treatment. Our findings demonstrate that systematic screening of tumors for oncogenic fusion genes will substantially improve the therapeutic prospects for a sizeable fraction of patients with PDAC. Advanced PDAC is a malignancy with few treatment options that lacks molecular mechanism-based therapies. Our study uncovers recurrent gene rearrangements such as fusions as disease-driving events in tumors, thereby providing novel insights into oncogenic signaling and new therapeutic options in this entity. .     «

We used whole-genome and transcriptome sequencing to identify clinically actionable genomic alterations in young adults with pancreatic ductal adenocarcinoma (PDAC). Molecular characterization of 17 patients with PDAC enrolled in a precision oncology program revealed gene fusions amenable to pharmacologic inhibition by small-molecule tyrosine kinase inhibitors in all patients with wild-type () tumors (4 of 17). These alterations included recurrent rearrangements predicted to drive PDAC develop...     »