Analysis of sporadic neuroendocrine rumours of the enteropancreatic systemby comparative genomic hybridisation

Background-Chromosomal instability is observed in a wide spectrum of human cancer syndromes. However, to date, little is known of the characteristic g enetic changes in sporadic neuroendocrine tumours of the gastroenteropancre atic system. Aims and method-We have studied copy number aberrations (CNAs) in 26 sporad ic neuroendocrine tumours of the enteropancreatic system (12 foregut and 14 midgut tumours) by comparative genomic hybridisation (CGH), allowing simul taneous evaluation of the entire tumour genome. Results-Nearly all tumours (25/26; that is, 96%) showed chromosomal imbalan ces, including full chromosomal aneuploidies, losses and gains of chromosom e arms, interstitial deletions, and amplifications. Whereas gains of chromo somes 4, 5, and 19 were found in both foregut and midgut tumours, gains of chromosomes 20q (58%), 19 (50%), as well as 17p (50%), and partial losses o f chromosomes Ip (42%), 2q (42%), 3p, 4q, and 6q (25% each) were frequently observed only in foregut tumours. In contrast, midgut tumours displayed le ss CNAs. Gains were detected for chromosomes 17q and 19p (57%). Most freque nt losses affected chromosomes 18 (43%) and 9p (21%). Conclusions-The results of our CGH analyses revealed new distinct candidate regions in the human genome associated with sporadic neuroendocrine tumour s. Some of the genetic alterations were shared by foregut and midgut tumour s while others discriminated between the two groups. Thus our results allud e to the involvement of identical as well as discriminative genetic loci in tumorigenesis and progression of neuroendocrine neoplasms of the foregut a nd midgut. Based on these findings potential new candidate genes will be di scussed.