Molecular Genetic Studies of Pancreatic Neuroendocrine Tumors: New Therapeutic Approaches

Endocrinol Metab Clin North Am. 2018 Sep;47(3):525-548. doi: 10.1016/j.ecl.2018.04.007.

Abstract

Pancreatic neuroendocrine tumors (PNETs) arise sporadically or as part of familial syndromes. Genetic studies of hereditary syndromes and whole exome sequencing analysis of sporadic NETs have revealed the roles of some genes involved in PNET tumorigenesis. The multiple endocrine neoplasia type 1 (MEN1) gene is most commonly mutated. Its encoded protein, menin, has roles in transcriptional regulation, genome stability, DNA repair, protein degradation, cell motility and adhesion, microRNA biogenesis, cell division, cell cycle control, and epigenetic regulation. Therapies targeting epigenetic regulation and MEN1 gene replacement have been reported to be effective in preclinical models.

Keywords: Epigenetic; MEN1; Menin; PNETs; RAS; SSTRs; VHL; mTOR.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Humans
  • Multiple Endocrine Neoplasia Type 1
  • Neuroendocrine Tumors / genetics*
  • Neuroendocrine Tumors / therapy*
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / therapy*
  • Proto-Oncogene Proteins / genetics

Substances

  • MEN1 protein, human
  • Proto-Oncogene Proteins