The molecular mechanisms responsible for the development and/or progression of gastrinomas are largely unknown. Studies involving sporadic enteropancreatic neuro-endocrine tumors suggest that mutations in the MEN1 gene occur in some tumors and probably play an important role in their pathogenesis. In this study, we examined whether somatic mutations in the MEN1 gene are also responsible for sporadic gastrinomas and correlate with clinical manifestations of gastrinomas in Japanese patients. Genomic DNA was extracted from paraffin-embedded gastrinoma tissues from 12 patients. Nucleotide sequences in the MEN1 genes were determined by direct sequencing. We identified 6 mutations in 7 out of 12 examined gastrinomas (58%). The identified mutations were 1 non-sense, 2 missense, 1 deletion leading to frame shifts, 1 insertion and 1 splicing mutation. Identical mutations were found in three gastrinoma tissues. The age at surgery, the rate of hepatic metastasis, and tumor status were not significantly different in the 2 groups. This study demonstrates that alterations in the MEN1 gene are involved in about half of all sporadic gastrinomas, although no correlation between the presence of mutations and location and clinical phenotype or severity of disease has been found.

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