Molecular drivers and cells of origin in pancreatic ductal adenocarcinoma and pancreatic neuroendocrine carcinoma
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Experimental Hematology & Oncology Open Access
REVIEW
Molecular drivers and cells of origin in pancreatic ductal adenocarcinoma and pancreatic neuroendocrine carcinoma He‑Li Gao1,2,3,4, Wen‑Quan Wang1,2,3,4, Xian‑Jun Yu1,2,3 and Liang Liu1,2,3,4*
Abstract Pancreatic cancer is one of the most common causes of cancer-related deaths worldwide. The two major histologi‑ cal 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-dif‑ ferentiated pancreatic neuroendocrine tumor and poorly-differentiated pancreatic neuroendocrine carcinoma (Pan‑ NEC). 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. Keywords: Pancreatic adenocarcinoma, Pancreatic neuroendocrine carcinoma, Neuroendocrine tumor, Carcinogenesis, Genomic patterns 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. Epidemiologic studies of all malignant types have shown that the 5-year relative survival rate is the lowest in PDAC and that death rates from this type of cancer have been rising over the past decade [1]. Less than 5% of patients with PDAC are alive after 5 years, and in patients discovered in the early stages, the 5-year survival rate is only approximately 20% [2]. The most common driver gene mutations of PDAC include KRAS, CDKN2A, TP53, and SMAD4, which all together account for 90% of cases [3].
*Correspondence: [email protected] 1 Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai 20032, People’s Republic of China Full list of author information is available at the end of the article
The second most common type of pancreatic neoplasm is pancreatic neuroendocrine neoplasm (PanNEN), which accounts for 3–5% of all cases [4]. It is important to note that poor differentiation of pancreatic neuroendocrine carcinoma (PanNEC) accounts for 10–20% of PanNEN cases. PanNEN has a prognosis similar to PDAC, with a median overall survival (OS) of only 7.5 months [5]. In contrast, well-differentiated pancreatic neuroendocrine tumors (PanNETs) are slow-growing with 5- and 15-year OS rates of 85.4% and 55%, respectively. In addition to distinguished clinicopathological characteristics and prognosis, PanNEC tumors are kno
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