Decoding the Molecular and Mutational Ambiguities of Gastroenteropancreatic Neuroendocrine Neoplasm Pathobiology
| Autor: | Mark Kidd, Irvin M. Modlin, Ignat Drozdov, Lisa Bodei |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
ISG
immature secretory vesicles Proliferation Review CgA chromogranin A Metastasis Transcriptome GEP-NEN gastroenteropancreatic neuroendocrine neoplasms CGH comparative genomic hybridization TGF transforming growth factor D cell somatostatin biology PI3K phosphoinositide-3 kinase Gastroenterology Chromogranin A MSI microsatellite instability cAMP adenosine 3′ 5′-cyclic monophosphate EC enterochromaffin Blood TSC2 tuberous sclerosis complex 2 (tuberin) VMAT vesicular monoamine transporters Protein kinase B signaling MEN-1/MEN1 multiple endocrine neoplasia type 1 Ki-67 miR/miRNA micro-RNA Somatostatin X/A-like cells ghrelin Gastroenteropancreatic Neuroendocrine Neoplasms NEN neuroendocrine neoplasms mTOR mammalian target of rapamycin Computational biology ERK extracellular-signal-regulated kinase PET positron emission tomography 5-HT serotonin 5-hydroxytryptamine SD-208 2-(5-chloro-2-fluorophenyl)-4-[(4-pyridyl)amino]p-teridine MTA metastasis associated-1 PI3 phosphoinositide-3 PKC protein kinase C medicine PTEN lcsh:RC799-869 LOH loss of heterozygosity Grading (tumors) SNV single-nucleotide variant PTEN phosphatase and tensin homolog deleted on chromosome 10 Hepatology IGF-I insulin-like growth factor-I TGN trans-Golgi network medicine.disease Carcinoid EGFR epidermal growth factor receptor GPCR G-protein coupled receptor NFκB nuclear factor κB SSA somatostatin analog ECL enterochromaffin-like Akt protein kinase B Cancer research biology.protein CREB cAMP response element-binding protein lcsh:Diseases of the digestive system. Gastroenterology PKA protein kinase A BRAF gene encoding serine/threonine-protein kinase B-Raf TSC2 G cell gastrin SST somatostatin DAG diacylglycerol GABA γ-aminobutyric acid MAPK mitogen-activated protein kinase Comparative genomic hybridization |
| Zdroj: | Cellular and Molecular Gastroenterology and Hepatology Cellular and Molecular Gastroenterology and Hepatology, Vol 1, Iss 2, Pp 131-153 (2015) |
| ISSN: | 2352-345X |
| DOI: | 10.1016/j.jcmgh.2014.12.008 |
| Popis: | Gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN), considered a heterogeneous neoplasia, exhibit ill-defined pathobiology and protean symptomatology and are ubiquitous in location. They are difficult to diagnose, challenging to manage, and outcome depends on cell type, secretory product, histopathologic grading, and organ of origin. A morphologic and molecular genomic review of these lesions highlights tumor characteristics that can be used clinically, such as somatostatin-receptor expression, and confirms features that set them outside the standard neoplasia paradigm. Their unique pathobiology is useful for developing diagnostics using somatostatin-receptor targeted imaging or uptake of radiolabeled amino acids specific to secretory products or metabolism. Therapy has evolved via targeting of protein kinase B signaling or somatostatin receptors with drugs or isotopes (peptide-receptor radiotherapy). With DNA sequencing, rarely identified activating mutations confirm that tumor suppressor genes are relevant. Genomic approaches focusing on cancer-associated genes and signaling pathways likely will remain uninformative. Their uniquely dissimilar molecular profiles mean individual tumors are unlikely to be easily or uniformly targeted by therapeutics currently linked to standard cancer genetic paradigms. The prevalence of menin mutations in pancreatic NEN and P27KIP1 mutations in small intestinal NEN represents initial steps to identifying a regulatory commonality in GEP-NEN. Transcriptional profiling and network-based analyses may define the cellular toolkit. Multianalyte diagnostic tools facilitate more accurate molecular pathologic delineations of NEN for assessing prognosis and identifying strategies for individualized patient treatment. GEP-NEN remain unique, poorly understood entities, and insight into their pathobiology and molecular mechanisms of growth and metastasis will help identify the diagnostic and therapeutic weaknesses of this neoplasia. Keywords: Gastroenteropancreatic Neuroendocrine Neoplasms, Blood, Carcinoid, Ki-67, Proliferation, Somatostatin, Transcriptome |
| Databáze: | OpenAIRE |
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