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J Clin Med. 2019 Aug 22;8(9). pii: E1277. doi: 10.3390/jcm8091277.

Updates on the Role of Molecular Alterations and NOTCH Signalling in the Development of Neuroendocrine Neoplasms.

Author information

1
Department of Abdominal Oncology, Istituto Nazionale Tumori, IRCCS Fondazione "G. Pascale", 80131 Naples, Italy.
2
Department of Surgery and Cancer, Imperial College London, London W12 0HS, UK.
3
Cancer Cell Metabolism Group. Centre for Haematology, Immunology and Inflammation Department, Imperial College London, London W12 0HS, UK.
4
SSD Innovative Therapies for Abdominal Metastases-Department of Abdominal Oncology, Istituto Nazionale Tumori, IRCCS-Fondazione "G. Pascale", 80131 Naples, Italy.
5
Department of Pathology, Istituto Nazionale Tumori, IRCCS-Fondazione "G. Pascale", 80131 Naples, Italy.
6
Unit of Molecular Biology and Viral Oncology, Department of Research, Istituto Nazionale Tumori IRCCS Fondazione Pascale, 80131 Naples, Italy. m.tornesello@istitutotumori.na.it.
7
Department of Abdominal Oncology, Istituto Nazionale Tumori, IRCCS Fondazione "G. Pascale", 80131 Naples, Italy. s.tafuto@istitutotumori.na.it.

Abstract

Neuroendocrine neoplasms (NENs) comprise a heterogeneous group of rare malignancies, mainly originating from hormone-secreting cells, which are widespread in human tissues. The identification of mutations in ATRX/DAXX genes in sporadic NENs, as well as the high burden of mutations scattered throughout the multiple endocrine neoplasia type 1 (MEN-1) gene in both sporadic and inherited syndromes, provided new insights into the molecular biology of tumour development. Other molecular mechanisms, such as the NOTCH signalling pathway, have shown to play an important role in the pathogenesis of NENs. NOTCH receptors are expressed on neuroendocrine cells and generally act as tumour suppressor proteins, but in some contexts can function as oncogenes. The biological heterogeneity of NENs suggests that to fully understand the role and the potential therapeutic implications of gene mutations and NOTCH signalling in NENs, a comprehensive analysis of genetic alterations, NOTCH expression patterns and their potential role across all NEN subtypes is required.

KEYWORDS:

NOTCH; cancer-driven genes; germline mutations; malignant castration-resistant prostatic cells; medullary thyroid carcinoma; mutational mechanism; neuroendocrine neoplasms; pancreatic NET; small bowel NET; small cell lung carcinoma

PMID:
31443481
DOI:
10.3390/jcm8091277
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