Molecular drivers and cells of origin in pancreatic ductal adenocarcinoma and pancreatic neuroendocrine carcinoma

He-Li Gao,Wen-Quan Wang,Xian-Jun Yu,Liang Liu

doi:10.1186/s40164-020-00184-0

Abstract

Pancreatic cancer is one of the most common causes of cancer-related deaths worldwide. The two major histological subtypes of pancreatic cancer are pancreatic ductal adenocarcinoma (PDAC), accounting for 90% of all cases, and pancreatic neuroendocrine neoplasm (PanNEN), which makes up 3–5% of all cases. PanNEN is classified into well-differentiated pancreatic neuroendocrine tumor and poorly-differentiated pancreatic neuroendocrine carcinoma (PanNEC). Although PDAC and PanNEN are commonly thought to be different diseases with distinct biology, cell of origin, and genomic abnormalities, the idea that PDAC and PanNEC share common cells of origin has been gaining support. This is substantiated by evidence that the molecular profiling of PanNEC is genetically and phenotypically related to PDAC. In the current review, we summarize published studies pointing to common potential cells of origin and speculate about how the distinct paths of differentiation are determined by the genomic patterns of each disease. We also discuss the overlap between PDAC and PanNEC, which has been noted in clinical observations.

Highlights

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of malignancy found in the pancreas, with over 90% of pancreatic neoplasms diagnosed as PDAC
pancreatic neuroendocrine carcinoma (PanNEC) tumors carry the mutations of tumor protein 53 (TP53), retinoblastoma 1 (RB1), and KRAS [6], which is similar to what is seen in PDAC, while differing completely from what occurs in pancreatic neuroendocrine tumors (PanNETs) [7]
Current data support the idea that the tumorigenesis of PanNEC and PDAC malignancies might overlap

Summary

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of malignancy found in the pancreas, with over 90% of pancreatic neoplasms diagnosed as PDAC. The most common driver gene mutations of PDAC include KRAS, CDKN2A, TP53, and SMAD4, which all together account for 90% of cases [3]. PanNEC tumors carry the mutations of tumor protein 53 (TP53), retinoblastoma 1 (RB1), and KRAS [6], which is similar to what is seen in PDAC, while differing completely from what occurs in PanNET [7].

Results

Conclusion