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 bioactive and hormonal products. Neuroendocrine tumors occur either sporadically or as part of familial syndromes (MEN1, MEN2). Defective DNA mismatch repair is implicated in a variety of gastrointestinal and other cancers; however, its role in the tumorigenesis of carcinoids has not been assessed. Formalin-fixed, paraffin-embedded archivial pathology tissues from 16 neuroendocrine tumors and 9 related metastases were studied by microdissection and microsatellite analysis of extracted DNA to evaluate the degree of microsatellite instability, a marker of defective mismatch repair. The carcinoid tumors analyzed display no microsatellite instability, but, interestingly, show a number of allelic deletions scattered throughout the genome. Particularly, the vast majority of pancreatic derived tumors display loss of heterozygosity on the short arm of chromosome 8. These results suggest that genomic instability is probably not involved in neuroendocrine carcinogenesis and a tumor suppressor gene involved in pancreatic carcinoid tumorigenesis could probably be localized on chromosome 8p12-22.
Department of Oncology, Division of Pathology, University of Pisa, I-56126 Pisa, Italy.
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C
Ghimenti
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Lonobile
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D
Campani
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G
Bevilacqua
M A
MA
Caligo
D000328:Adult; D000368:Aged; D000483:Alleles; D005260:Female; D015894:Genome, Human; D006801:Humans; D007150:Immunohistochemistry; D007414:Intestinal Neoplasms / Q000235:genetics*; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics*; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics*