Microsatellite instability and allelic losses in neuroendocrine tumors of the gastro-entero-pancreatic system

Carcinoids are well differentiated tumors, able to secrete a variety of bio active and hormonal products. Neuroendocrine tumors occur either sporadical ly or as part of familial syndromes (MEN1, MEN2). Defective DNA mismatch re pair is implicated in a variety of gastrointestinal and other cancers; howe ver, its role in the tumorigenesis of carcinoids has not been assessed. For malin-fixed, paraffin-embedded archivial pathology tissues from 16 neuroend ocrine tumors and 9 related metastases were studied by microdissection and microsatellite analysis of extracted DNA to evaluate the degree of microsat ellite instability, a marker of defective mismatch repair. The carcinoid tu mors analyzed display no microsatellite instability, but, interestingly, sh ow a number of allelic deletions scattered throughout the genome. Particula rly, the vast majority of pancreatic derived tumors display loss of heteroz ygosity on the short arm of chromosome 8. These results suggest that genomi c instability is probably not involved in neuroendocrine carcinogenesis and a tumor suppressor gene involved in pancreatic carcinoid tumorigenesis cou ld probably be localized on chromosome 8p12-22.