(Epi)genetic landscape of neuroendocrine neoplasms

Subtitle:moving towards liquid biopsies

Neuroendocrine neoplasms (NENs) are malignancies that develop from neuroendocrine cells present in various organs throughout the human body, including pancreas, small intestine and lung. They are historically considered rare, but their incidence has been increasing over the past decades. An important unmet medical need are good, preferably blood-based, biomarkers that can assist in the clinical management of NEN patients. Advances in next-generation sequencing and other high-throughput technologies have accelerated the molecular research in NENs. Newly identified molecular alterations could therefore provide a novel and interesting source of biomarkers for NENs and warrant further study. In this PhD project, we have therefore explored the genetic and epigenetic landscape of NENs with the general aim of identifying both tissue and liquid biomarkers. In a proof-of-concept study, we first examined the presence of circulating tumor DNA (ctDNA) in plasma of pancreatic NEN (PNEN) patients using mutation and copy number alteration profiling. In a follow-up study, the biomarker potential of ctDNA was further explored in a larger cohort of gastroenteropancreatic and lung NEN patients of which longitudinal plasma samples were collected. In the last part, the epigenetic landscape was studied, and more specifically the genome-wide DNA methylation profile of PNENs. Thereby, PDX1 DNA methylation was studied as a biomarker for PNEN subtyping.

Publication year:2021

Keywords:Doctoral thesis

Accessibility:Open