ONCOGENE PANEL SEQUENCING ANALYSIS IDENTIFIES CANDIDATE ACTIONABLE GENES IN ADVANCED WELL-DIFFERENTIATED GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS

Abstract Purpose to report the rate of candidate actionable somatic mutations in patients with locally advanced and metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NET) and of other genetic alterations that may be associated with tumorigenesis Methods A phase II mutation targeted therapy trial was conducted in patients with advanced well differentiated G1/G2 GEP-NETs. Mutations found in mTOR pathway associated genes, led to treatment with the mTOR inhibitor everolimus, and were defined as actionable. Tumor DNA from GEP-NETs were sequenced and compared with germline DNA, using the OncoVar-NET assay, designed for hybrid capture sequencing of 500 tumor suppressor genes and oncogenes. Somatic variants were called, and copy-number (CN) variant analysis was performed. Results Thirty patients (14 small-intestine, 8 pancreatic, 3 unknown primary NETs and 5 of other primary sites), harbored 37 lesions (4 patients had DNA of multiple lesions sequenced). Only 2 patients with sporadic NET (n=26) had an a...