This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tanaka, C. Articles by Itakura, M. Search for Related Content PubMed PubMed Citation Articles by Tanaka, C. Articles by Itakura, M.

Absence of Germ-Line Mutations of the Multiple Endocrine Neoplasia Type 1 (MEN1) Gene in Familial Pituitary Adenoma in Contrast to MEN1 in Japanese¹

Otsuka Department of Clinical and Molecular Nutrition, The University of Tokushima School of Medicine, 3–18-15, Kuramoto-cho, Tokushima-City, 770; Department of Neurosurgery, Toranomon Hospital (S.Y.), 2–2-2, Toranomon, Minato-ku, Tokyo, 105; and Department of Neurosurgery, Tokyo Medical College (H.N.), 6–7-1, Nishishinjuku, Shinjuku-ku, Tokyo, 160 Japan

Address all correspondence and requests for reprints to: Mitsuo Itakura, M.D., Ph.D., Otsuka Department of Clinical and Molecular Nutrition, The University of Tokushima School of Medicine, 3–18-15, Kuramoto-cho, Tokushima-City, 770, Japan. E-mail: itakura{at}nutr.med.tokushima-u.ac.jp

Germ-line mutations of the MEN1 gene were analyzed in five cases of familial and four cases of sporadic multiple endocrine neoplasia type 1 (MEN-1), six cases in three independent pedigrees of familial pituitary adenoma without MEN-1, and three cases of familial isolated primary hyperparathyroidism (FIHP) in Japanese. Eight different types of germ-line mutations in all nine cases of MEN-1 were distributed in exons 2, 3, 7, and 10 and intron 7 of the MEN1 gene. Loss of heterozygosity (LOH) on 11q13 was detected in all nine tumors of these cases with microsatellite analysis. No germ-line mutation of the MEN1 gene was detected in three pedigrees of familial pituitary adenoma and three cases of FIHP. LOH on 11q13 was detected in two cases in one pedigree of familial pituitary adenoma, and one of them showed a heterozygous somatic mutation of the MEN1 gene. No LOH on 11q13 was detected in three cases of FIHP. Based on these, we conclude that the loss of function of menin is etiological for familial or sporadic MEN-1, but not for FIHP or most familial pituitary adenoma without MEN-1.

This article has been cited by other articles:

				X.-H. Jiang, J.-L. Lu, B. Cui, Y.-J. Zhao, W.-q. Wang, J.-M. Liu, W.-Q. Fang, Y.-N. Cao, Y. Ge, C.-x. Zhang, et al. MEN1 mutation analysis in Chinese patients with multiple endocrine neoplasia type 1 Endocr. Relat. Cancer, December 1, 2007; 14(4): 1073 - 1079. [Abstract] [Full Text] [PDF]

				R. A. Toledo, D. M. Lourenco Jr., B. Liberman, M. B. C. Cunha-Neto, M. G. Cavalcanti, C. B. Moyses, S. P. A. Toledo, and P. L. M. Dahia Germline Mutation in the Aryl Hydrocarbon Receptor Interacting Protein Gene in Familial Somatotropinoma J. Clin. Endocrinol. Metab., May 1, 2007; 92(5): 1934 - 1937. [Abstract] [Full Text] [PDF]

				V. M. Howell, J. W. Cardinal, A.-L. Richardson, O. Gimm, B. G. Robinson, and D. J. Marsh Rapid Mutation Screening for HRPT2 and MEN1 Mutations Associated with Familial and Sporadic Primary Hyperparathyroidism J. Mol. Diagn., November 1, 2006; 8(5): 559 - 566. [Abstract] [Full Text] [PDF]

				O. Vierimaa, M. Georgitsi, R. Lehtonen, P. Vahteristo, A. Kokko, A. Raitila, K. Tuppurainen, T. M. L. Ebeling, P. I. Salmela, R. Paschke, et al. Pituitary Adenoma Predisposition Caused by Germline Mutations in the AIP Gene. Science, May 26, 2006; 312(5777): 1228 - 1230. [Abstract] [Full Text] [PDF]

				B. S. Soares, K. Eguchi, and L. A. Frohman Tumor Deletion Mapping on Chromosome 11q13 in Eight Families with Isolated Familial Somatotropinoma and in 15 Sporadic Somatotropinomas J. Clin. Endocrinol. Metab., December 1, 2005; 90(12): 6580 - 6587. [Abstract] [Full Text] [PDF]

				C. A. Carrasco, A. A. Gonzalez, C. A. Carvajal, C. Campusano, E. Oestreicher, E. Arteaga, N. Wohllk, and C. E. Fardella Novel Intronic Mutation of MEN1 Gene Causing Familial Isolated Primary Hyperparathyroidism J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 4124 - 4129. [Abstract] [Full Text] [PDF]

				W. F. Simonds, C. M. Robbins, S. K. Agarwal, G. N. Hendy, J. D. Carpten, and S. J. Marx Familial Isolated Hyperparathyroidism Is Rarely Caused by Germline Mutation in HRPT2, the Gene for the Hyperparathyroidism-Jaw Tumor Syndrome J. Clin. Endocrinol. Metab., January 1, 2004; 89(1): 96 - 102. [Abstract] [Full Text] [PDF]

				A Cebrian, S Ruiz-Llorente, A Cascon, M Pollan, J J Diez, A Pico, D Telleria, J Benitez, and M Robledo Mutational and gross deletion study of the MEN1 gene and correlation with clinical features in Spanish patients J. Med. Genet., May 1, 2003; 40(5): e72 - 72. [Full Text] [PDF]

				B. Verges, F. Boureille, P. Goudet, A. Murat, A. Beckers, G. Sassolas, P. Cougard, B. Chambe, C. Montvernay, and A. Calender Pituitary Disease in MEN Type 1 (MEN1): Data from the France-Belgium MEN1 Multicenter Study J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 457 - 465. [Abstract] [Full Text] [PDF]

				M. L. Brandi, R. F. Gagel, A. Angeli, J. P. Bilezikian, P. Beck-Peccoz, C. Bordi, B. Conte-Devolx, A. Falchetti, R. G. Gheri, A. Libroia, et al. CONSENSUS: Guidelines for Diagnosis and Therapy of MEN Type 1 and Type 2 J. Clin. Endocrinol. Metab., December 1, 2001; 86(12): 5658 - 5671. [Abstract] [Full Text] [PDF]

				S. S. Guo and M. P. Sawicki Molecular and Genetic Mechanisms of Tumorigenesis in Multiple Endocrine Neoplasia Type-1 Mol. Endocrinol., October 1, 2001; 15(10): 1653 - 1664. [Abstract] [Full Text] [PDF]

				T. Abe, K. Yoshimoto, M. Taniyama, K. Hanakawa, H. Izumiyama, M. Itakura, and K. Matsumoto An Unusual Kindred of the Multiple Endocrine Neoplasia Type 1 (MEN1) in Japanese J. Clin. Endocrinol. Metab., March 1, 2000; 85(3): 1327 - 1330. [Full Text]

				M. R. Gadelha, K. N. Une, K. Rohde, M. Vaisman, R. D. Kineman, and L. A. Frohman Isolated Familial Somatotropinomas: Establishment of Linkage to Chromosome 11q13.1-11q13.3 and Evidence for a Potential Second Locus at Chromosome 2p16-12 J. Clin. Endocrinol. Metab., February 1, 2000; 85(2): 707 - 714. [Abstract] [Full Text]

				M. Kassem, T. A. Kruse, F. K. Wong, C. Larsson, and B. T. Teh Familial Isolated Hyperparathyroidism as a Variant of Multiple Endocrine Neoplasia Type 1 in a Large Danish Pedigree J. Clin. Endocrinol. Metab., January 1, 2000; 85(1): 165 - 167. [Abstract] [Full Text]

				P. L. M. Dahia and A. B. Grossman The Molecular Pathogenesis of Corticotroph Tumors Endocr. Rev., April 1, 1999; 20(2): 136 - 155. [Abstract] [Full Text]

				M. R. Gadelha, T. R. Prezant, K. N. Une, R. P. Glick, S. F. Moskal II, M. Vaisman, S. Melmed, R. D. Kineman, and L. A. Frohman Loss of Heterozygosity on Chromosome 11q13 in Two Families with Acromegaly/Gigantism Is Independent of Mutations of the Multiple Endocrine Neoplasia Type I Gene J. Clin. Endocrinol. Metab., January 1, 1999; 84(1): 249 - 256. [Abstract] [Full Text]

				C. Tanaka, T. Kimura, P. Yang, M. Moritani, T. Yamaoka, S. Yamada, T. Sano, K. Yoshimoto, and M. Itakura Analysis of Loss of Heterozygosity on Chromosome 11 and Infrequent Inactivation of the MEN1 Gene in Sporadic Pituitary Adenomas J. Clin. Endocrinol. Metab., August 1, 1998; 83(8): 2631 - 2634. [Abstract] [Full Text]

				B. Mayr, G. Brabant, and A. v. z. Mühlen Menin Mutations In MEN1 Patients J. Clin. Endocrinol. Metab., August 1, 1998; 83(8): 3004 - 3005. [Full Text]