Abstract 2253: Comparison of genomic alterations in neuroendocrine tumors originated from different primary sites

Abstract

Abstract Background: Neuroendocrine tumors (NETs) are heterogeneous, relatively rare tumors derive from neuroendocrine system. Currently, limited therapeutic strategies are available for NETs. Next-generation sequencing (NGS) and target gene-based precision therapy have shown promising efficacy in many tumors, but fare in NETs. Several reports illustrated that the primary sites of NETs were significantly bound up with the clinical response and prognosis. However, characteristics of their genomic alterations are insufficiency nowadays. Methods: A cohort of 94 Chinese NET patients were recruited, and the FFPE tumor tissues and matching blood samples from different primary sites were collected. Targeted next generation sequencing (NGS) of 450 genes was performed in OrigiMed (Shanghai, China) with a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. Results: In all patients, the top 5 most-frequently aberrant genes were TP53 (46.8%, 44/94), RB1 (23.4% 22/94), MEN1 (20.2%, 19/94), KRAS (11.7%, 11/94) and ATRX (9.6%, 9/94). The enrolled NETs contain 7 different primary sites, namely, 37 pancreatic NETs (PNETs), 16 hepatic NETs (HNETs), 11 gastric NETs (GNETs), 10 gallbladder NETs (GB-NETs), 8 esophageal NETs (ENETs), 7 colorectal NETs (CNETs), and 5 small intestine NETs (SI-NETs). Based on origin sites, TP53 is the most widely distributed mutant gene in all sites except for PNETs (Ranked 3rd), while RB1 mutations were significantly higher in ENETs (75.0%, 6/8), GB-NETs (60.0%, 6/10) and GNETs (36.4%, 4/11). Other higher -frequency mutated genes among different sites showed greatly dissimilarity (MEN1, ATRX and DAXX in PNETs; FAT3, MAX, MUC16, GATA4 and OBSCN in HNETs; APC, KRAS and PTEN in GNETs; TERT, ERBB2 and YES1 in GB-NETs; LRP1B and FBXW7 in ENETs; APC, ADGRA2 and FGFR1 in CNETs; NF1 in SI-NETs). Furthermore, signaling pathways involved in potential drug-target genes were analyzed. Results revealed 16.0% (15/94) patients with aberrations in PI3K/AKT/mTOR pathway, 11.7% (11/94) in Cell-Cycle pathway, 9.6% (9/94) in HRD pathway, 9.6% (9/94) in FGF pathway and 16.0% (15/94) in other cancer-related genes (ERBB2, VHL, MET etc.). Conclusions: This study reveals the genomic alteration characteristics of NETs from different primary sites. The profiles obtained in our study may provide evidences for further targeted therapy to improve outcomes of Chinese NETs. Citation Format: Qiyun Tang, Ye Tian, Xiaolin Li, Jian'an Bai, Min Liu, Ping Hu, Shanshan Zhang, Zanmei Xu, Yueting Qu, Aodi Wang. Comparison of genomic alterations in neuroendocrine tumors originated from different primary sites [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2253.