Genetics of pancreatic neuroendocrine tumors: implications for the clinic

Abstract

Pancreatic neuroendocrine tumors (PanNETs) are a common and deadly neoplasm of the pancreas. Although the importance of genetic alterations in PanNETs has been known for many years, recent comprehensive sequencing studies have greatly expanded our knowledge of neuroendocrine tumorigenesis in the pancreas. These studies have identified specific cellular processes that are altered in PanNETs, highlighted alterations with prognostic implications, and pointed to pathways for targeted therapies. In this review, we will discuss the genetic alterations that play a key role in PanNET tumorigenesis, with a specific focus on those alterations with the potential to change the way patients with these neoplasms are diagnosed and treated.

Pancreatic Neuroendocrine Tumor Invading the Stomach and Spleen: A Case Report

“…PNET can be functioning (hormone-hypersecreting) or non-functioning. Insulinomas are the most common functioning PNETs, followed by gastrinomas, glucagonomas, somatostatinomas and VIPomas [3]. Patients with functioning PNET commonly present in earlier stages with symptoms due to hormone hypersecretion.…”

“…Patients with functional PNET typically have a favorable prognosis because they are diagnosed at earlier stages. Approximately 90% of PNETs are sporadic, whereas 10% are observed in patients with a familial endocrine tumor syndrome [3]. These syndromes include multiple endocrine neoplasia 1 (MEN1), tuberous sclerosis, neurofibromatosis type 1 and von Hippel-Lindau disease.…”

Assessment of pancreatic neuroendocrine tumor cytologic genotype diversity to guide personalized medicine using a custom gastroenteropancreatic next-generation sequencing panel

“…Sporadic and familial pNETs are understudied tumors that follow a hyperplasia to neoplasia sequence. [ 23 ] As precision medicine is rapidly becoming the “Holy Grail” to customize individual patient care, little is known of their cytologic genetic signature and how that may deliver prognostic or predictive biomarkers for disease management. Research efforts have been challenging as access to tissue from a broad spectrum of disease stages and cell lines has been limited which is compounded by the fact that these tumors have alterations at a much lower frequency when compared to PDAC.…”

Surgical and molecular pathology of pancreatic neoplasms

“…Therapeutically, PanNETs relying on angiogenesis are theoretically targetable by blocking specific pathway components (e.g. VEGF inhibitors) [ 105 – 107 ]. Similarly, PanNETs relying on mTOR activation should be particularly susceptible to everolimus, a drug which has shown to significantly prolong survival [ 108 ].…”