Evaluation of germline mutations in TSC2 and other genes related to hereditary syndromes in gastroenteropancreáticas neuroendocrine tumors

Abstract

Gastroenteropancreatic neuroendocrine tumors (GEP-NET) have their origin in cells of the diffuse neuroendocrine system, present throughout the gastrointestinal tract and in pancreas. Although relatively rare, compared to adenocarcinoma of the gastrointestinal tract, important advances in diagnostics have made their incidence increase in recent decades which, associated with indolent behavior in a subgroup of patients, make this entity of increasing relevance. Most GEP-NET are sporadic events, however, 5 to 10% of patients have a family history suggestive of syndromes. In a study by this team of researchers, 7 patients had their primary neuroendocrine tumor sequenced. In 2 cases deleterious mutations were identified in TSC2, which was later confirmed to be of germline origin. None of these patients had suggestive history of familial predisposition to cancer or phenotype of tuberous sclerosis. The primaryobjective of the study is to define the prevalence of germline mutations in TSC2 in patients with GEP-NET. The secondary objective is to determine, in the same population, the frequency of germline mutations associated with other genetic syndromes predisposing to NET (genes MEN1, RET, VHL, NF1, TSC1, TP 53 and FLCN). The cohort of this study will be 96 patients, treated at HSL or ICESP, with histological diagnosis of neuroendocrine cancer, for which there is clinical information. The blood will be collected and the buffy coat will have its DNA extracted. The genes of interest will be evaluated through amplicon capture-based, followed by sequencing in next-generation platform (Illumina). Clinicopathological data of the study population and information of molecular analysis, will be analyzed using descriptive statistics, and subsequently compared with the data available in the scientific literature. (AU)