MEN1 gene mutations in sporadic neuroendocrine tumors of foregut derivation

Foregut-derived neuroendocrine (NE) tumors occur sporadically or in associa tion with multiple endocrine neoplasia type 1 (MEN1) syndrome. Thirty-nine sporadic NE tumors of foregut derivation (six thymic, 21 bronchial, three g astric, and nine pancreatic tumors) as well as two hindgut-derived rectal c arcinoids for somatic MEN1 gene mutation were analyzed by direct sequencing analysis. Five tumors showed mutations: nonsense mutations (Q393X and R98X ) in thymic and pancreatic NE tumors, respectively, a 4 b.p. deletion (357d el4) in a gastric NE carcinoma, and missense mutations (D172Y and S178Y) in pancreatic NE tumors, No mutation was identified in pulmonary or rectal NE tumors. In a patient with a pancreatic NE tumor (D172Y), the corresponding germline DNA showed the same mutation, suggesting that sporadic MEN1 syndr ome was masked in this case, Somatic MEN1 gene mutations and deletions may play a crucial role in the tumorigenesis of a subset of foregut-derived NE tumors, Sporadic MEN1 syndrome may occur as a sporadic NE tumor of the panc reas.