Blood-based next-generation sequencing analysis of neuroendocrine neoplasms.

• Type of Material: Article
• Authors: Katerina Zakka, Emory University; Rebecca Nagy, Guardant Health Inc.; Leylah Drusbosky, Guardant Health Inc.; Mehmet Akce, Emory University; Christina Wu, Emory University; Olatunji Alese, Emory University; Bassel El-Rayes, Emory University; Pashtoon Murtaza Kasi, University of Iowa; Kabir Mody, Mayo Clinic; Jason Starr, Mayo Clinic; Walid Shaib, Emory University
• Language: English
• Date: 2020-05-12
• Publisher: Impact Journals
• Publication Version: Final Published Version
• Copyright Statement: © 2020 Zakka et al.
• License: Creative Commons Attribution 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.18632/oncotarget.27588
• Title of Journal or Parent Work: Oncotarget
• ISSN: 1949-2553
• Volume: 11
• Issue: 19
• Start Page: 1749
• End Page: 1757
• Grant/Funding Information: There was no specific funding for this study and there are no competing financial disclosures.
• Keywords: neuroendocrine tumor; neuroendocrine neoplasm; next-generation sequencing; neuroendocrine carcinoma; circulating tumor DNA
• Research Categories: Biology, Neuroscience

Abstract

Background: Neuroendocrine neoplasms (NENs) are a heterogeneous group of neoplasms that span from well-differentiated neuroendocrine tumors (NETs) to highly aggressive neoplasms classified as neuroendocrine carcinomas (NECs). The genomic landscape of NENs has not been well studied. The aim of this study is to confirm the feasibility of next generation sequencing (NGS) testing circulating tumor DNA (ctDNA) in patients with NENs and characterize common alterations in the genomic landscape. Results: Of the 320 NEN patients, 182 (57%) were male with a median age of 63 years (range: 8-93) years. Tumor type included pancreatic NET (N = 165, 52%), gastrointestinal NEC (N = 52, 16%), large cell lung NEC (N = 21, 7%), nasopharyngeal NEC (N = 16, 5%) and NEC/NET not otherwise specified (N = 64, 20%). ctDNA NGS testing was performed on 338 plasma samples; 14 patients had testing performed twice and 2 patients had testing performed three times. Genomic alterations were defined in 280 (87.5%) samples with a total of 1,012 alterations identified after excluding variants of uncertain significance (VUSs) and synonymous mutations. Of the 280 samples with alterations, TP53 associated genes were most commonly altered (N = 145, 52%), followed by KRAS (N = 61, 22%), EGFR (N = 33, 12%), PIK3CA (N = 30, 11%), BRAF (N = 28, 10%), MYC (N = 28, 10%), CCNE1 (N = 28, 10%), CDK6 (N = 22, 8%), RB1 (N = 19, 7%), NF1 (N = 19, 7%), MET (N = 19, 7%), FGFR1 (N = 19, 7%), APC (N = 19, 7%), ERBB2 (N = 16, 6%) and PTEN (N = 14, 5%). Conclusions: Evaluation of ctDNA was feasible among individuals with NEN. Liquid biopsies are non-invasive methods that can provide personalized options for targeted therapies in NEN patients. Patients and Methods: Molecular alterations in 338 plasma samples from 320 patients with NEN were evaluated using clinical-grade NGS of ctDNA (Guardant360®) across multiple institutions. The test detects single nucleotide variants in 54-73 genes, copy number amplifications, fusions, and indels in selected genes.