NANETS2025 18th Annual Multidisciplinary NET Medical Symposium NANETS 2025 Other Section (13 abstracts)
Molecular and Clinical Profiling of Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs): An Analysis of the Oncology Research Information Exchange Network Database
Benjamin E Ueberroth 1 , Patrick M Boland 2 , Michael Cavnar 3 , Melissa Fishel 4 , Michele M Gage 5 , Deepak Vadehra 6 , Tiago Biachi de Castria 7 , Dae Won Kim 7 , Ashish Manne 8 , Bodour Salhia 9 , Julia White 10 , Carlos Chan 11 , Muneeb Rehman 12 , Hassan Hatoum 13 , Hannah R Robinson 1 , S Lindsey Davis 1 , Christopher H Lieu 1 , Nicole B Balmaceda 1 , Alexander Hayden 1 , Alexis D Leal 1 , Sunnie S Kim 1 , Robert W Lentz 1 , Wells A Messersmith 1 & Emily Baiyee Toegel 1
1University of Colorado Cancer Center, Aurora, CO; 2Rutgers University Robert Wood Johnson School of Medicine, Newark, NJ; 3University of Kentucky Markey Cancer Center, Lexington, KY; 4University of Indiana Simon Cancer Center, Indianapolis, IN; 5Murtha Cancer Center, Bethesda, MD; 6Roswell Park Cancer Center, Buffalo, NY; 7Moffitt Cancer Center, Tampa, FL; 8Ohio State University School of Medicine, Columbus, OH; 9University of Southern California Keck School of Medicine, Los Angeles, CA; 10University of Kansas Cancer Center, Kansas City, KS; 11University of Iowa Holden Cancer Center, Iowa City, IA; 12University of Virginia Comprehensive Cancer Center, Charlottesville, VA; 13Oklahoma University Stephenson Cancer Center
Background: The incidence of neuroendocrine tumors (NETs) is approximately 7 per 100,000 persons and rising. By location, tumors located in the gastroenteropancreatic (GEP) region, particularly midgut NETs, are most common. The Oncology Research Information Exchange Network (ORIEN) database contains complementary clinical, genomic, and transcriptomic profiling, providing opportunities to identify novel associations between molecular features and clinical outcomes.
Methods: Survival analyses were performed using the Log-rank testing, and clinical features were evaluated using Wilcoxon and chi-squared tests. Mutational analyses utilized sample-level enrichments from whole exome sequencing data, and statistical tests were performed using the one-sided Fisher Exact test. Transcriptomic analyses utilized a student’s t-test. We reviewed well-differentiated GEP-NET samples of these primary sites: pancreatic (n = 121), small bowel (n = 89), gastric (n = 15), and colorectal (n = 9). A p-value <0.05 was considered significant.
Results: Across all GEP-NETs, the most common somatic mutations were TTN (29%), MUC16 (25%), TGIF2LX (23%), CCDC168 (21%), MUC17 (18%), and MEN1 (18%). The most common copy number amplifications were MUC3A (61%), PRSS2 (32%), ROCK1P1 (30%), and MUC19 (30%). NETs of small bowel origin had significantly higher rates of M1 stage than pancreatic NETs (P = 0.02). Quantitative MSI by WES was significantly higher in pNETs compared to sbNETs (P < 0.001). MEN1 was the most common mutation in pNETs (35.6%). Mutations in ARGAP (23%), CEP126 (22%), MMP20 (17%), CASP5 (17%), DDI1 (15%), and TRPC6 (15%) were the most common in sbNETs and none of these were frequent in pNETs. pNETS with a mutation in ATRX and/or DAXX had significantly higher rates of M1 disease than ATRX/DAXXwt pNETs (P = 0.029). Specifically, the liver was a more common site of metastatic disease in ATRX/DAXXmut pNETS compared to ATRX/DAXXwt. More than 200 distinct mRNA expression levels by WES were significantly different between ATRX/DAXXmut and wt, potentially providing additional information on the prognostic role of ATRX/DAXX mutations in pNETs.
Conclusions: We report the first clinical, genomic, and transcriptomic analysis of ORIEN GEP-NET cases. These findings create multiple avenues for further investigation and reinforce the value of multi-institutional consortia such as ORIEN in deepening our knowledge of well-differentiated NETs.
Abstract ID #33678
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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