Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuroendocrine cancer cell lines are used to investigate therapeutic targets in neuroendocrine tumors (NET) and have been instrumental in the design of clinical trials targeting the PI3K/AKT/mTOR pathways, VEGF inhibitors, and somatostatin analogues. It remains unknown, however, whether the genomic makeup of NET cell lines reflect that of primary NET since comprehensive unbiased genome sequencing has not been performed on the cell lines. Four bronchopulmonary NET (BP-NET)-NCI-H720, NCI-H727, NCI-H835, and UMC11-and two pancreatic neuroendocrine tumors (panNET)-BON-1 and QGP1-were cultured. DNA was isolated, and exome sequencing was done. GATK and EXCAVATOR were used for bioinformatic analysis. We detected a total of 1,764 nonsynonymous single nucleotide variants at a rate of 8 per Mb in BP-NET and 4.3 per Mb in panNET cell lines, including 52 mutated COSMIC cancer genes in these cell lines, such as TP53, BRCA1, RB1, TSC2, NOTCH1, EP300, GNAS, KDR, STK11, and APC but not ATRX, DAXX, nor MEN1. Our data suggest that mutation rate, the pattern of copy number variations, and the mutational spectra in the BP-NET cell lines are more similar to the changes observed in small cell lung cancer than those found in primary BP-NET. Likewise, mutation rate and pattern including the absence of mutations in ATRX/DAXX, MEN1, and YY1 in the panNET cell lines BON1 and QGP1 suggest that these cell lines do not have the genetic signatures of a primary panNET. These results suggest that results from experiments with BP-NET and panNET cell lines need to be interpreted with caution.
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PMID:Exome-level comparison of primary well-differentiated neuroendocrine tumors and their cell lines. 2634 99

Somatostatin receptor 2A expression is a feature of well-differentiated neuroendocrine neoplasms and is important for their diagnosis and therapy. Little is known about somatostatin receptor 2A expression in poorly differentiated neuroendocrine neoplasms in relation to TP53 and RB1 status and how these features may contribute to the separation of well from poorly differentiated neuroendocrine neoplasms with a proliferation index above 20%. This study investigates the expression of somatostatin receptors, p53 and Rb1, and TP53 alterations in pancreatic and extrapancreatic well and poorly differentiated neuroendocrine neoplasms (Ki67-index >20%). Thirty-seven poorly differentiated neuroendocrine neoplasms of pancreatic (n=12) and extrapancreatic origin (n=25) as well as 10 well-differentiated neuroendocrine neoplasms of the pancreas (n=9) and rectum (n=1) with a Ki67-index >20% were immunostained for synaptophysin, chromogranin A, Ki67, CD56, p53, Rb1, ATRX, DAXX, progesterone receptor, somatostatin receptor 2A, somatostatin receptor 5, and cytokeratin 20, and sequenced for TP53, exons 5-9. Somatostatin receptor 2A was positive in 6/37 of poorly differentiated and in 8/10 of well-differentiated neuroendocrine neoplasms. One well-differentiated and two poorly differentiated neuroendocrine neoplasms expressed somatostatin receptor 5. Abnormal nuclear p53 and Rb1 staining was found in 29/37 and 22/37 poorly differentiated neuroendocrine neoplasms, respectively, whereas all well-differentiated neuroendocrine neoplasms showed normal p53 and Rb1 expression. TP53 gene alterations were restricted to poorly differentiated neuroendocrine neoplasms (24/34) and correlated well with p53 expression. All cases were progesterone receptor negative. Somatostatin receptor 2A expression is not limited to well-differentiated neuroendocrine neoplasms but also occurs in 16% of poorly differentiated neuroendocrine neoplasms from various sites. Most poorly differentiated neuroendocrine neoplasms are characterized by TP53 alterations and Rb1 loss, usually in the absence of somatostatin receptor 2A expression. In the pancreas, these criteria contribute to separate well-differentiated neuroendocrine neoplasms with a Ki67-index above 20% from poorly differentiated neuroendocrine neoplasms.
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PMID:Somatostatin receptor expression related to TP53 and RB1 alterations in pancreatic and extrapancreatic neuroendocrine neoplasms with a Ki67-index above 20. 2805 98

Pancreatic neuroendocrine neoplasms (panNENs) are the second most common epithelial tumors of the pancreas. Despite improvements in prognostic grading and staging systems, it remains a challenge to predict the clinical behavior of panNENs and the response to specific therapies given the high degree of heterogeneity of these tumors. Most panNENs are nonfunctional and present as advanced disease. However, systemic therapies provide modest benefits. Therefore, there is a need for predictive biomarkers to develop personalized treatment and to advance new drug development. The somatostatin receptors remain the only clinically established prognostic and predictive biomarkers in panNENs. Oncogenic drivers are at a very low frequency. Commonly mutated genes in panNENs include MEN1, chromatin remodeling genes (DAXX and ATRX), and mammalian target of rapamycin pathway genes. In contrast, poorly differentiated neuroendocrine carcinomas (panNECs), which carry a very poor prognosis, have distinctive mutations in certain genes (eg, RB1 and p53). Ongoing research to integrate epigenomics will provide tremendous opportunities to improve current understanding of the clinical heterogeneity of pancreatic neuroendocrine tumors and provide invaluable insight into the biology of these tumors, new drug development, and establishing personalized therapies.
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PMID:Molecular profile of pancreatic neuroendocrine neoplasms (PanNENs): Opportunities for personalized therapies. 3327 Sep 5