Multi-omic molecular profiling of pancreatic neuroendocrine tumors.

Abstract

e15685 Multi-omic Molecular profiling of Pancreatic Neuroendocrine Tumors Authors: Rishi R Patel, Joseph Bender, Quanlin, Dana Pan, Lynn Matrisian, David Halverson, Emanuel Petricoin, Subha Madhavan, Richard Tuli, Michael Pishvaian, Andrew Hendifar; Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA Background: Pancreatic Neuroendocrine Tumors (pNETs) are a rare malignancy with an incidence of 2 per 1,000,000. In 2016, the Pancreatic Cancer Action Network and Perthera initiated the Know Your Tumor (KYT) initiative in an effort to improve coordination across clinical spectrums in regards to multi-omic molecular profiling and clinical outcomes data pertaining to pancreatic tumors. We used data collected as part of the KYT effort to describe demographic, clinical and genomic data for pNETs. Methods: From 2015 - 2016, 15 patients with pNET were enrolled in the KYT program, which helped facilitate tissue acquisition, clinical data collection, and multi-omic molecular profiling. Using the data collected, we performed Fisher’s Exact to assess for statistical significance between genetic alterations and histology. Results: 11/15 of our patients were female. 8/15 had metastatic disease at the time of diagnosis, while 5/15 had locally advanced disease at the time of diagnosis. 29 genetic alterations were pathogenic. KMT2D and MEN1 were jointly found in 6/15 of our patients. 5/15 with pathogenic alterations in p53, 2/15 with DAXX, 5/15 with alteration in RB1, and 2/15 with alterations in PTEN and TSC2. 2 patients had pathologic alterations in mismatch repair genes, MLH1 and MSH1. Two genes had a statistically significant relationship to pNET histology. Alterations in MEN1 (p = 0.0097) and SPTA1 (p = 0.0333) were associated with high grade tumors (p = 0.0097). Of note, both of the patients under the age of 35 shared an alteration in ATR, which none of the other enrollees expressed. Conclusions: In PNETS, multi-omic profiling through the KYT program identified targetable alterations in several key pathways. Outcome data will be explored.