Positional Cloning of the Gene for Multiple Endocrine Neoplasia-Type 1

• Published in: Science (American Association for the Advancement of Science) Vol. 276; no. 5311; pp. 404 - 407
• Main Authors: Chandrasekharappa, Settara C., Guru, Siradanahalli C., Manickam, Pachiappan, Olufemi, Shodimu-Emmanuel, Collins, Francis S., Emmert-Buck, Michael R., Debelenko, Larisa V., Zhuang, Zhengping, Lubensky, Irina A., Liotta, Lance A., Crabtree, Judy S., Wang, Yingping, Roe, Bruce A., Weisemann, Jane, Boguski, Mark S., Agarwal, Sunita K., Kester, Mary Beth, Kim, Young S., Heppner, Christina, Dong, Qihan, Spiegel, Allen M., Burns, A. Lee, Marx, Stephen J.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 18.04.1997; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Adenomatosis, Familial endocrine; Amino Acid Sequence; Biological and medical sciences; Cancer; Chromosome Mapping; Chromosomes, Human, Pair 11; Clones; Cloning; Cloning, Molecular; DNA; DNA, Complementary - genetics; Endocrinopathies; Exons; Frameshift Mutation; Gels; Genes; Genes, Tumor Suppressor; Genetic mutation; Genomics; Humans; Innovations; Males; Malignant tumors; Medical research; Medical sciences; Molecular Sequence Data; Multiple endocrine neoplasia; Multiple endocrine neoplasia type 1; Multiple Endocrine Neoplasia Type 1 - genetics; Mutation; Neoplasm Proteins - chemistry; Neoplasm Proteins - genetics; Polymerase chain reaction; Proto-Oncogene Proteins; Sequencing; Thyroid. Thyroid axis (diseases); Transcripts (Written Records); Tumors; Endocrinopathy; Genetic mapping; Human; Nucleotide sequence; Homology; Gene organization; Carcinogenesis; Chromosome C11; Genetic disease; Multiple endocrine neoplasia type I; Complementary DNA; Benign neoplasm; Mutation; Tumor suppressor gene
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.276.5311.404

Multiple endocrine neoplasia-type 1 (MEN1) is an autosomal dominant familial cancer syndrome characterized by tumors in parathyroids, enteropancreatic endocrine tissues, and the anterior pituitary. DNA sequencing from a previously identified minimal interval on chromosome 11q13 identified several candidate genes, one of which contained 12 different frameshift, nonsense, missense, and in-frame deletion mutations in 14 probands from 15 families The MEN1 gene contains 10 exons and encodes a ubiquitously expressed 2.8-kilobase transcript. The predicted 610-amino acid protein product, termed menin, exhibits no apparent similarities to any previously known proteins. The identification of MEN1 will enable improved understanding of the mechanism of endocrine tumorigenesis and should facilitate early diagnosis.