title: Analysis of molecular pathways in neuroendocrine cancers of the gastroenteropancreatic system.
abstract: Neuroendocrine gastroenteropancreatic (GEP) tumors are rare and present with variable clinical syndromes. So far, there are no detailed studies concerning the molecular pathogenesis of sporadic GEP tumors. In our study, GEP tumors from 29 patients were assessed for microsatellite instability, aberrant promoter methylation, and LOH of various tumor suppressor genes. All tumors were microsatellite stable. One tumor showed LOH close to the APC locus, one tumor had an allelic loss near the hMLH1 gene, and one tumor showed hypermethylation of the hMLH1 promoter. Interestingly, none of the tumors was aberrantly methylated at the p16 promoter. However, 13 of 20 successfully amplified tumors (65%) were hypermethylated at the APC promoter. Of the hypermethylated tumors, none showed LOH of either the hMLH1 or the APC gene. The current study is the first report demonstrating that aberrant methylation of the APC promoter is strongly involved in the molecular tumorigenesis of neuroendocrine GEP tumors. MSI does not seem to be involved in the pathogenesis of these cancers. Further studies are required to investigate the role of hypermethylation in neuroendocrine GEP tumors and to further elucidate the role of the APC pathway in these tumors.
authors.affiliation: Medizinische Universitätsklinik Freiburg, Abteilung Innere Medizin II, Freiburg, Germany. arnold@medl.ukl.uni-freiburg.de
authors.forename: Christian N
authors.initials: CN
authors.lastname: Arnold
authors.forename: Andrea
authors.initials: A
authors.lastname: Sosnowski
authors.forename: Hubert E
authors.initials: HE
authors.lastname: Blum
mesh_terms: D019175:DNA Methylation; D005770:Gastrointestinal Neoplasms / Q000235:genetics* / Q000503:physiopathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D018358:Neuroendocrine Tumors / Q000235:genetics* / Q000503:physiopathology; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000503:physiopathology