title: Localization of sporadic neuroendocrine tumors by gene expression analysis of their metastases.
abstract: A characteristic of human gastroenteropancreatic neuroendocrine tumors (GEP-NET) is a minute unobtrusive primary tumor which often cannot be detected by common physical examinations. It therefore remains unidentified until the tumor has spread and space-occupying metastases cause clinical symptoms leading to diagnosis. Cases in which the primary cannot be located are referred to as NET with CUP-syndrome (cancer of unknown primary syndrome). With the help of array-CGH (comparative genomic hybridization, Agilent 105K) and gene expression analysis (Agilent 44K), microdissected primaries and their metastases were compared to identify up- and down-regulated genes which can be used as a marker for tumor progression. In a next analysis step, a hierarchical clustering of 41.078 genes revealed three genes [C-type lectin domain family 13 member A (CD302), peptidylprolyl isomerase containing WD40 repeat (PPWD1) and abhydrolase domain containing 14B (ABHD14B)] which expression levels can categorize the metastases into three groups depending on the localization of their primary. Because cancer therapy is dependent on the localization of the primary, the gene expression level of these three genes are promising markers to unravel the CUP syndrome in NET.
authors.affiliation: Core Unit Chip Application, Institute of Human Genetics, UKJ, University Hospital Jena, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Posorski
authors.forename: Daniel
authors.initials: D
authors.lastname: Kaemmerer
authors.forename: Guenther
authors.initials: G
authors.lastname: Ernst
authors.forename: Patricia
authors.initials: P
authors.lastname: Grabowski
authors.forename: Dieter
authors.initials: D
authors.lastname: Hoersch
authors.forename: Merten
authors.initials: M
authors.lastname: Hommann
authors.forename: Ferdinand
authors.initials: F
authors.lastname: von Eggeling
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000556:secondary* / Q000628:therapy; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D009382:Neoplasms, Unknown Primary / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018358:Neuroendocrine Tumors / Q000235:genetics* / Q000473:pathology / Q000556:secondary* / Q000628:therapy; D020411:Oligonucleotide Array Sequence Analysis