Genetics and Epigenetics of Gastroenteropancreatic Neuroendocrine Neoplasms.
Journal
Endocrine reviews
ISSN: 1945-7189
Titre abrégé: Endocr Rev
Pays: United States
ID NLM: 8006258
Informations de publication
Date de publication:
01 04 2019
01 04 2019
Historique:
received:
24
06
2018
accepted:
27
12
2018
pubmed:
19
1
2019
medline:
15
8
2019
entrez:
19
1
2019
Statut:
ppublish
Résumé
Gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs) are heterogeneous regarding site of origin, biological behavior, and malignant potential. There has been a rapid increase in data publication during the last 10 years, mainly driven by high-throughput studies on pancreatic and small intestinal neuroendocrine tumors (NETs). This review summarizes the present knowledge on genetic and epigenetic alterations. We integrated the available information from each compartment to give a pathway-based overview. This provided a summary of the critical alterations sustaining neoplastic cells. It also highlighted similarities and differences across anatomical locations and points that need further investigation. GEP-NENs include well-differentiated NETs and poorly differentiated neuroendocrine carcinomas (NECs). NENs are graded as G1, G2, or G3 based on mitotic count and/or Ki-67 labeling index, NECs are G3 by definition. The distinction between NETs and NECs is also linked to their genetic background, as TP53 and RB1 inactivation in NECs set them apart from NETs. A large number of genetic and epigenetic alterations have been reported. Recurrent changes have been traced back to a reduced number of core pathways, including DNA damage repair, cell cycle regulation, and phosphatidylinositol 3-kinase/mammalian target of rapamycin signaling. In pancreatic tumors, chromatin remodeling/histone methylation and telomere alteration are also affected. However, also owing to the paucity of disease models, further research is necessary to fully integrate and functionalize data on deregulated pathways to recapitulate the large heterogeneity of behaviors displayed by these tumors. This is expected to impact diagnostics, prognostic stratification, and planning of personalized therapy.
Identifiants
pubmed: 30657883
pii: 5289720
doi: 10.1210/er.2018-00160
pmc: PMC6534496
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Pagination
506-536Informations de copyright
Copyright © 2019 Endocrine Society.
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