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Arnold CN, Sosnowski A, Schmitt-Graff A, et al. Analysis of molecular pathways in sporadic neuroendocrine tumors of the gastro-entero- pancreatic system. Int J Cancer 2007; 120:2157-2164. This study is presenting genetic alterations as well as the CpG island methylation phenotype (CIMP). Significant differences in promoter hypermethylation were identified in the RUNX3 and the O6-MGMT gene. They could also demonstrate correlation between CIMP and the Ki-67 index above 10% indicating a prognostic relevance for both of them.
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Arnold CN, Sosnowski A, Schmitt-Graff A, et al. Analysis of molecular pathways in sporadic neuroendocrine tumors of the gastro-entero- pancreatic system. Int J Cancer 2007; 120:2157-2164. This study is presenting genetic alterations as well as the CpG island methylation phenotype (CIMP). Significant differences in promoter hypermethylation were identified in the RUNX3 and the O6-MGMT gene. They could also demonstrate correlation between CIMP and the Ki-67 index above 10% indicating a prognostic relevance for both of them.
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61
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Tannapfel A, Vomschloss S, Karhoff D, et al. BRAF gene mutations are rare events in gastroenteropancreatic neuroendocrine tumors. Am J Clin Pathol 2005; 123:256-260.
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Fujiki K, Duerr EM, Kikuchi H, et al. Hoxc6 is overexpressed in gastrointestinal carcinoids and interacts with JunD to regulate tumor growth. Gastroenterology 2008; 135:907-916; discussion 916 e901-e902. The homeobox gene Hoxc6 was highly upregulated in human gastrointestinal carcinoid tumors. By establishing carcinoid cells that stably overexpressed Hoxc6 or were deficient of Hoxc6 cellular proliferation assay, luciferase reporter assays, western blotting, immunoprecipitation, DNA affinity precipitation and DNA microarray could demonstrate that Hoxc6 overexpression stimulates the cell proliferation and knockdown inhibited their growth. Hoxc6 activated the oncogenic activator protein-1 signaling pathway through a physical interaction with JunD. Hoxc6 also induced the expression of genes that characteristically are upregulated in carcinoid tumors including neurotensin and connected tissue growth factors
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Fujiki K, Duerr EM, Kikuchi H, et al. Hoxc6 is overexpressed in gastrointestinal carcinoids and interacts with JunD to regulate tumor growth. Gastroenterology 2008; 135:907-916; discussion 916 e901-e902. The homeobox gene Hoxc6 was highly upregulated in human gastrointestinal carcinoid tumors. By establishing carcinoid cells that stably overexpressed Hoxc6 or were deficient of Hoxc6 cellular proliferation assay, luciferase reporter assays, western blotting, immunoprecipitation, DNA affinity precipitation and DNA microarray could demonstrate that Hoxc6 overexpression stimulates the cell proliferation and knockdown inhibited their growth. Hoxc6 activated the oncogenic activator protein-1 signaling pathway through a physical interaction with JunD. Hoxc6 also induced the expression of genes that characteristically are upregulated in carcinoid tumors including neurotensin and connected tissue growth factors.
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66
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Kidd M, Modlin IM, Mane SM, et al. The role of genetic markers - NAP1L1, MAGE-D2, and MTA1 - in defining small-intestinal carcinoid neoplasia. Ann Surg Oncol 2006; 13:253-262.
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Berkovic MC, Jokic M, Marout J, et al. IL-6-174 C/G polymorphism in the gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Exp Mol Pathol 2007; 83:474-479. This study is reporting on IL-6 in 80 patients with GEP-NETs. IL-6 is a pleiotropic cytokine with a still controversial role in tumorigenesis of different cancer types. This study is reporting about higher serum IL-6 values in GEP-NETs patients compared with healthy controls (36.8%). Phenotype analysis showed that the majority of the patients had genotype GG IL-6-174. This correlation between serum IL-6 values and the IL-6-174 genotype was particularly significant in nonfunctioning GEP-NETs.
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Berkovic MC, Jokic M, Marout J, et al. IL-6-174 C/G polymorphism in the gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Exp Mol Pathol 2007; 83:474-479. This study is reporting on IL-6 in 80 patients with GEP-NETs. IL-6 is a pleiotropic cytokine with a still controversial role in tumorigenesis of different cancer types. This study is reporting about higher serum IL-6 values in GEP-NETs patients compared with healthy controls (36.8%). Phenotype analysis showed that the majority of the patients had genotype GG IL-6-174. This correlation between serum IL-6 values and the IL-6-174 genotype was particularly significant in nonfunctioning GEP-NETs.
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68
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Modlin IM, Oberg K, Chung DC, et al. Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol 2008; 9:61-72. This study is reviewing the current status of tumor biology and clinical management of gastroenteropancreatic neuroendocrine tumors. This study is summarizing the requirements for an improvement in neuroendocrine tumors outcome with refinement of the universal classification and grading system. The study further elucidates the cell biology, development of cell lines and animal models, acquisition of genetic information and identification of serum marker for early diagnosis. Furthermore, definition of tissue markers to identify tumor origin and the molecular pathology profiling to define prognosis are needed in the future.
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Modlin IM, Oberg K, Chung DC, et al. Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol 2008; 9:61-72. This study is reviewing the current status of tumor biology and clinical management of gastroenteropancreatic neuroendocrine tumors. This study is summarizing the requirements for an improvement in neuroendocrine tumors outcome with refinement of the universal classification and grading system. The study further elucidates the cell biology, development of cell lines and animal models, acquisition of genetic information and identification of serum marker for early diagnosis. Furthermore, definition of tissue markers to identify tumor origin and the molecular pathology profiling to define prognosis are needed in the future.
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69
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Molecular profiles of gastroenteropancreatic endocrine tumors
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This study is summarizing the current knowledge in the molecular profiles of GEP-NET tumors
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Perren A, Anlauf M, Komminoth P. Molecular profiles of gastroenteropancreatic endocrine tumors. Virchows Arch 2007; 451 (Suppl 1):S39-S46. This study is summarizing the current knowledge in the molecular profiles of GEP-NET tumors.
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Virchows Arch
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Perren, A.1
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Komminoth, P.3
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