MEN1 gene mutations in sporadic neuroendocrine tumors of foregut derivation.
Foregut-derived neuroendocrine (NE) tumors occur sporadically or in association with multiple endocrine neoplasia type 1 (MEN1) syndrome. Thirty-nine sporadic NE tumors of foregut derivation (six thymic, 21 bronchial, three gastric, and nine pancreatic tumors) as well as two hindgut-derived rectal carcinoids 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 (357del4) 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 syndrome 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 pancreas.
Fujii
T
T
Department of Pathology, Jichi Medical School, Minamikawachi, Kawachi, Tochigi, Japan. tfujii@jichi.ac.jp
Kawai
T
T
Saito
K
K
Hishima
T
T
Hayashi
Y
Y
Imura
J
J
Hironaka
M
M
Hosoya
Y
Y
Koike
M
M
Fukayama
M
M
D000328:Adult; D000368:Aged; D001984:Bronchial Neoplasms / Q000235:genetics; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D018095:Germ-Line Mutation; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics*; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics*; D018358:Neuroendocrine Tumors / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics; D011518:Proto-Oncogene Proteins; D013274:Stomach Neoplasms / Q000235:genetics; D013953:Thymus Neoplasms / Q000235:genetics
D004273:DNA, Neoplasm; C105373:MEN1 protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins