Related Experiment Video
Updated: Nov 12, 2025
Author Spotlight: Finding New Therapeutic Targets for Malignant Peripheral Nerve Sheath Tumor Through Genome-Scale shRNA Screens
Published on: August 25, 2023
Mutational landscape and potential therapeutic targets for sporadic pancreatic neuroendocrine tumors based on target
Kailian Zheng1, Tao Liu2, Jiangman Zhao3,4
1Department of General Surgery, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, P.R. China.
Abstract:
Pancreatic neuroendocrine tumor (PNET), a heterogenous type of neoplasm with limited treatment options, is relatively rare and to date, the genetic background has remained to be fully elucidated. The present study aimed to determine the mutational landscape of PNET with and without liver metastasis, as well as its clinical application value for treatment. Fresh tumor tissues were collected from 14 patients with PNET following surgery, 4 of whom had developed liver metastasis. Subsequently, targeted next-generation sequencing of 612 cancer-associated genes and comprehensive analysis were performed on the tumor tissues. The results identified 63 somatic mutations in 53 genes in the 14 patients with PNET, amongst which menin 1 was identified as the most recurrently mutated gene. The analysis also identified several novel recurrently mutated genes, including adrenoceptor alpha 2B, ARVCF delta catenin family member, carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase and neuregulin 1. Among the 53 mutated genes, 11 were enriched in the PI3K/AKT signaling pathway (adjusted P=7.12x10-5). In addition, 4 patients with PNET with liver metastasis had distinctly different mutational profiles compared with those without liver metastasis; 13 genes were discovered to be exclusively mutated in the liver metastasis group of the patients with PNET, including ATRX chromatin remodeler, thioredoxin reductase 2, anus kinase 3, ARVCF delta catenin family member, integrin subunit alpha V and RAD50 double strand break repair protein. In addition, two potentially actionable alterations in BRCA2 DNA repair-associated (p.Q548Q) and neurofibromin 1 (p.Q1188X) were identified using the OncoKB database. In conclusion, the present study generated a comprehensive mutational profile of 14 patients with PNET and further described the features of patients with liver metastasis, which highlights potential targets for drug development of PNET.
Insights
This study reveals the genetic mutations in pancreatic neuroendocrine tumors (PNETs), identifying key genes and pathways involved in liver metastasis. These findings highlight potential new therapeutic targets for PNET treatment.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Pancreatic neuroendocrine tumors (PNETs) are rare neoplasms with limited treatment options.
- The genetic underpinnings of PNET development and metastasis remain incompletely understood.
Purpose of the Study:
- To determine the mutational landscape of PNETs with and without liver metastasis.
- To identify potential therapeutic targets for PNET treatment.
Main Methods:
- Targeted next-generation sequencing of 612 cancer-associated genes was performed on 14 PNET tumor tissues.
- Comprehensive mutational analysis was conducted, including comparison between PNETs with and without liver metastasis.
Main Results:
- 63 somatic mutations in 53 genes were identified, with MEN1 being the most recurrently mutated gene.
- Distinct mutational profiles were observed in PNETs with liver metastasis, with 13 genes exclusively mutated in this group.
- Eleven mutated genes were enriched in the PI3K/AKT signaling pathway; actionable alterations in BRCA2 and NF1 were identified.
Conclusions:
- This study provides a comprehensive mutational profile of PNETs, particularly highlighting genetic differences in the presence of liver metastasis.
- The identified mutations and enriched pathways offer potential targets for novel drug development in PNET treatment.
