Comprehensive Molecular Analysis Identifies Driver Mutations in Metastases of Sporadic Well-Differentiated Neuroendocrine Tumours of the Small Intestine Abstract #2982

Introduction: Small intestinal neuroendocrine tumours (SI-NETs) represent a heterogenous group of tumours. The molecular mechanisms which contribute to progression of SI-NETs are poorly elucidated. They are considered to be molecularly distinct from neuroendocrine carcinomas (NECs), which share oncogenic pathways with adenocarcinomas.
Aim(s): To perform a comprehensive genetic characterization of metastatic SI-NETs.
Materials and methods: Whole genome sequencing (WGS) of 35 and next generation sequencing (NGS) of 8 metastasized SI-NET was performed. Biopsies were taken between 2016 and 2019. Tumours were classified using the latest WHO classification (2018). WGS included assessment of somatic mutations in all cancer related driver genes, tumour mutational burden (TMB) and microsatellite status. NGS entailed a diagnostic cancer hotspot mutation panel of 58 genes. Our cohort consisted of 21% G1, 65% G2 and 14% G3 well-differentiated metastasized SI-NETs.
Conference: 17th Annual ENETS Conference 2020 (2020)
Category: Basic Science - Genetics, epigenetics, miRNAs, Omics
Presenting Author: Drs Kris Samsom

To read results and conclusion, please login ...

Further abstracts you may be interested in

#20 Paraneoplastic antigen Ma2 (PNMA2) auto-antibodies as biomarkers for early small intestine neuroendocrine tumors detection
Introduction: Small intestine neuroendocrine tumors (NETs) comprise well-differentiated NET (benign carcinoid), well-differentiated neuroendocrine carcinoma (malignant carcinoid) and poorly differentiated neuroendocrine carcinoma (NEC). The majority of NET patients have developed liver metastases at the time of diagnosis and surgery is then seldom curative. Novel predictive, diagnostic and prognostic markers are thus needed to improve our capabilities to diagnose and cure these tumors. We have previously identified six novel marker genes for neuroendocrine tumor cells by using Affymetrix microarrays and advanced bioinformatics. One of this markers, the paraneoplastic antigen Ma2 (PNMA2), which is normally expressed only in nervous tissue, can in the process of carcinogenesis be detected in tumors located outside the nervous system. The finding that Ma2 is expressed in small intestine neuroendocrine primary tumors and their metastases made it interesting to screen whether antibodies against Ma2 are present in the serum of NET patients.
Conference: 7th Annual ENETS Conference (2010)
Category: Basic
Presenting Author: PhD Valeria Giandomenico
Authors: Cui T, Elgue G, Li S C, Hurtig M, ...
#62 Genome-wide DNA methylation profiling of pancreatic neuroendocrine tumors identifies distinct methylation profiles and differentially methylated gene promoter regions associated with low, medium and high grade tumors
Introduction: Integration of genetics and epigenetics has emerged as a powerful approach to studying cellular differentiation (Mikkelsen et al, 2009) and tumorigenesis (Shen et al, 2007). The study of DNA methylation is of particular importance in cancer, as causal involvement has been demonstrated and it is the most stable of all epigenetic modifications, making it a desirable marker for both early detection and treatment of tumors. Hypermethylation of CpG sites in gene promoter regions leads to decreased gene expression; if such a gene is a tumor suppressor, this leads to carcinogenesis. To date, there have been no studies of genome-wide DNA methylation profiling of NETs. This study sets out to determine the DNA methylation profiles of low, intermediate and high grade pancreatic NET liver metastases with the intention of identifying dysregulated biological pathways in the development of these tumors. A protocol for the analysis formalin-fixed paraffin embedded tissue (FFPE) has also been developed in order to study these tumors in significant numbers following this pilot study.
Conference: 7th Annual ENETS Conference (2010)
Category: Basic
Presenting Author: Dr Christina Thirlwell
#200 Genome-Wide MicroRNA Expression in Small Intestine Neuroendocrine Tumors (“Midgut carcinoids”): Upregulation of miRNA-182, miRNA-183 and Downregulation of miRNA-215
Introduction: MicroRNAs (miRs) may regulate cell proliferation, differentiation, apoptosis and function as tumor suppressors or oncogenes. MiR expression is not characterized in neuroendocrine midgut carcinoids.
Conference: 8th Annual ENETS Conference (2011)
Category: Basic
Presenting Author: PhD student Su-Chen Li
#316 Utilization of Gene Network Graph Topology with Inference Relevance Analysis Delineates G Protein-coupled Receptor Pathways and CREB Targets in Small Intestinal Neuroendocrine Neoplasia
Introduction: Despite an increasing incidence, a paucity of biological information has led to major limitations in identification of plausible therapeutic targets for small intestinal neuroendocrine tumors (SINETs)
Conference: 8th Annual ENETS Conference (2011)
Category: Basic
Presenting Author: Dr Mark Kidd
#355 MicroRNA Signatures as Novel Biomarkers in Small Intestine Neuroendocrine Tumors
Introduction: Small intestine (SI) neuroendocrine tumors (NET) arise from serotonin-producing intraepithelial cells in the SI referred to as enterochromafin cells. The detection of SI-NETs is often concomitant with the appearance of hepatic metastasis thus most patients with SI-NET have metastases at initial presentation. MicroRNAs (miRs) are post-transcriptional key regulators in tumorigenesis which regulate expression of other genes. Little evidence of miR expression or deregulation in SI-NETs has been reported.
Category: Basic
Presenting Author: Su-Chen Li
Authors: Li S C, Ahmed E, Martijn C, Lloyd R, ...