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Molecular Genetic Studies of Pancreatic Neuroendocrine Tumors: New Therapeutic Approaches

Abstract:
Pancreatic neuroendocrine tumors (PNETs) can occur as sporadic neoplasms or as part of hereditary syndromes such as multiple endocrine neoplasia type 1 (MEN1). MEN1, which is an autosomal dominant disorder, is due to loss-of-function mutations of the tumor suppressor MEN1 gene that encodes menin. Approximately 40% of nonfamilial (ie, sporadic) PNETs have MEN1 mutations, with subsequent loss of menin, which acts as a tumor suppressor. Menin is a scaffold protein with roles in transcriptional regulation, genome stability, DNA repair, protein degradation, cell motility and adhesion, microRNA biogenesis, cell division, cell cycle control, epigenetic regulation, and Wnt signaling. Emerging therapies targeting the functional roles of menin with Men1 gene replacement therapy, epigenetic modulators, and antagonists of Wnt-signaling may prove useful for future treatment of PNETs.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1016/j.ecl.2018.04.007

Authors

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Institution:
University of Oxford
Division:
MSD
Department:
RDM
Sub department:
OCDEM
Oxford college:
Keble College
Role:
Author



Publisher:
Elsevier
Host title:
Endocrinology and Metabolism Clinics of North America
Publication date:
2018-08-08
DOI:
ISSN:
0889-8529


Keywords:
Pubs id:
pubs:857229
UUID:
uuid:60df3b77-b1b7-4623-80a0-57ba33ce58d9
Local pid:
pubs:857229
Source identifiers:
857229
Deposit date:
2018-06-15
ARK identifier:

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