Two novel mutations are identified in the MEN1 gene from nine archived paraffin-embedded neuroendocrine tumors, demonstrating that retrospective genetic analysis can be used to identify mutations in the MEN1 gene from preserved tissue.
Insulinomas (pancreatic islet β cell tumors) are the most common type of functioning pancreatic neuroendocrine tumors that occur sporadically or as a part of the MEN1 syndrome that is caused by germ line mutations in MEN1.
Menin, the product of the Men1 gene, which is frequently mutated in pancreatic neuroendocrine tumors, acts as a chromatin-remodeling factor to modulate the transcription of cell cycle regulators by interacting with histone modification factors.
Finally, the clinical applications provided by the understanding of the effects of MEN1 gene mutations on neuroendocrine tumor development in patients with this familial cancer syndrome are discussed.
Neuroendocrine tumors (NETs) of the pancreas (PNETs) and bronchus (BNETs), which may have 5-year survivals of <50% and as low as 5%, respectively, represent targets for such drugs, as >40% of PNETs and ~35% of BNETs have mutations of the multiple endocrine neoplasia type 1 (MEN1) gene, which encodes menin that modifies histones by interacting with histone methyltransferases.
A germline mutation of the MEN1 gene was detected, and deletions of the MEN1 gene were consistently detected in multiple neuroendocrine tumors involving the parathyroid glands and the pancreas and a hepatic neuroendocrine tumor metastasis, as predicted by Knudson's "two hit" hypothesis.
Allelic deletion of the MEN1 locus was identified in 18/49 (36.7%) tumors (13/30, 43.3% in EPT and 5/19, 26.3% in NET) and mutations of the MEN1 gene were present in 8/52 (15.3%) tumors (4/30 (13.3%) EPT and 4/22 (18.1%) NET).
The MEN1 gene locus is known to be partly responsible for the tumorigenesis of sporadic gastric neuroendocrine tumors, but the genetic events that drive the neoplastic process of this tumor remain largely unknown.
Rats affected by the MENX (MEN1-like) syndrome share some features with MEN1 patients albeit they bear a germline mutation in <i>Cdkn1b</i> (p27) and not in <i>Men1</i> Both <i>Men1</i>-knockout mice and MENX rats have been exploited for therapy-response studies testing novel drugs for efficacy against neuroendocrine tumors (NETs) and have provided promising leads for novel therapies.
Somatostatin receptor 2 (SSTR2) is frequently overexpressed on several types of solid tumors, including neuroendocrine tumors and small-cell lung cancer.
Further studies on a larger cohort of pituitary carcinomas are needed to clarify whether ATRX mutations may contribute to the metastatic potential in a subset of pituitary NETs.
KRAS and DAXX/ATRX gene mutations are correlated with the clinicopathological features, advanced diseases, and poor prognosis in Chinese patients with pancreatic neuroendocrine tumors.