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Decoding the genetic puzzle: Mutations in key driver genes of pancreatic neuroendocrine tumors

Huanchang Jiang1, Wuhu Zhang1, Xiaowu Xu1

  • 1Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Shanghai Pancreatic Cancer Institute, Shanghai 200032, China; Shanghai Key Laboratory of Precision Medicine for Pancreatic Cancer, Shanghai 200032, China; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China.

Biochimica Et Biophysica Acta. Reviews on Cancer
|March 30, 2025
PubMed

Insights

Pancreatic neuroendocrine tumors (PanNETs) have distinct genetic profiles, including mutations in MEN1, ATRX, DAXX, and VHL. Understanding these genetic alterations aids in developing targeted therapies for improved patient outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Pancreatic neuroendocrine tumors (PanNETs) are rare but exhibit unique clinical and genetic characteristics.
  • Advances in sequencing technology have enhanced the understanding of PanNET molecular pathways.

Purpose of the Study:

  • To review the pathogenesis of PanNETs by examining key genetic mutations.
  • To clarify the clinical relevance of these mutations for potential therapeutic strategies.

Main Methods:

  • Review of current literature on PanNET genetics and molecular pathways.
  • Analysis of frequently mutated genes including MEN1, ATRX, DAXX, VHL, PTEN, TSC1/TSC2, and AKT1-3.

Main Results:

  • MEN1 mutations affect tumor suppressor menin, impacting gene regulation and DNA repair.
  • ATRX and DAXX alterations are linked to chromatin remodeling, telomere stability, and aggressive tumor behavior via the ALT pathway.
  • VHL mutations highlight the roles of hypoxia and angiogenesis.
  • Mutations in PTEN, TSC1/TSC2, and AKT1-3 disrupt the mTOR pathway, contributing to PanNET complexity.

Conclusions:

  • Genetic alterations in PanNETs significantly influence tumor behavior and therapeutic responses.
  • Understanding the PI3K/AKT/mTOR pathway and other genetic disruptions is crucial for developing novel targeted therapies.
  • Targeted therapies based on specific genetic profiles hold promise for improving patient prognosis in PanNETs.
Keywords:
ATRXDAXXMEN1Pancreatic cancerVHLmTOR

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