SOMATIC MUTATIONS OF THE MEN1 TUMOR-SUPPRESSOR GENE IN SPORADIC GASTRINOMAS AND INSULINOMAS

Gastrinomas and insulinomas are frequent in multiple endocrine neoplas ia type 1 (MEN1), The MEN1 tumor suppressor gene was recently identifi ed. To elucidate the etiological role of the MEN1 gene in sporadic ent eropancreatic endocrine tumorigenesis, we analyzed tumors (28 gastrino mas and 12 insulinomas) from 40 patients for MEN1 gene mutations and a llelic deletions. One copy of the MEN1 gene was found to be deleted in 25 of 27 (93%) sporadic gastrinomas and in 6 of 12 (50%) sporadic ins ulinomas. MEN1 gene mutations were identified in 9 of 27 (33%) sporadi c gastrinomas and 2 of 12 (17%) insulinomas and were not seen in corre sponding germ-line DNA sequence, A specific MEN1 mutation was detected in one gastrinoma and in the corresponding germ-line DNA of a patient who had no family history of MEN1. Somatic MEN1 gene mutations and de letions play a critical role in the tumorigenesis of sporadic gastrino mas and may also contribute to the development of a subgroup of insuli nomas.