Neuroendocrine cells are present in the hormone-producing glands of the endocrine system, originating from the neuroectoderm. In the gastrointestinal tract, normal neuroendocrine cells regulate absorption, motility, secretion, and affect cellular proliferation. Neuroendocrine tumors (NETs) are a collection of a large variation of tumors originating from these cells, known for being unpredictable and irregular in their phenotype. Due to the great variation and delayed diagnosis, treatment may not be optimal, and knowledge of individualized treatment and precision medicine is lacking. Small intestinal neuroendocrine tumors (SI-NETs) originate from the enterochromaffin cells in the gastrointestinal tract, are often slow-growing and small in size with an annual incidence of 1 per 100 000. Most patients show obscure symptoms, and metastases are commonly found in the liver and proximal lymph nodes by the time of diagnosis. Results from studies on epigenetic and genetic alterations in SI-NETs are scarce, and extensive DNA analysis using short-read sequencing (SRS) and array-based methods has revealed a stable tumor phenotype with no recurrent mutations. SI-NETs possess fewer mutations than other cancers and the most common structural variation (SV) is due to somatic copy number alteration resulting in the loss of heterozygosity of chromosome. Single nucleotide variants (SNV) have been found in SMAD-related genes. Epigenetic changes are believed to be playing an important role in tumorigenesis, as up to 70% of the SI-NETs are believed to be epigenetically dysregulated. However, for the majority of SI-NETs, events and driver mutations leading to oncogenesis remain unknown. Using long-read sequencing (LRS) technologies such as Oxford Nanopore Technologies Inc. (ONT) makes it possible to resolve complex SVs and repeats. It allows us to analyze long-range haplotypes, phasing, mutational SNVs and epigenetic changes through methylation alterations. In cancer studies, SV- and methylation analysis are crucial for discovering new mechanisms and driver genes involved in oncogenesis. Genome-wide hypomethylation, as well as hypermethylation of CpG islands associated with tumor suppressor genes and developmental regulators are characteristic of cancer cells. SV discovery is challenging using SRS methods due to the characteristics of short fragments. Long reads can cover SV breakpoints or entire SV events, and this has been proven to be well suited for sequencing GC-rich and large genomic regions found in SVs, repetitive elements, and complex regions. To this date, SI-NET genomes have not been investigated with the LRS approach. Therefore, we will apply long-read sequencing on a selected, well-characterized SI-NET sample group originating from our biobank cohort.