This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart 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 Kjellman, M. Articles by Larsson, C. Search for Related Content PubMed PubMed Citation Articles by Kjellman, M. Articles by Larsson, C.

Genotyping of Adrenocortical Tumors: Very Frequent Deletions of the MEN1 Locus in 11q13 and of a 1-Centimorgan Region in 2p16¹

Departments of Surgery (M.K., L.-O.F., M.B.), Molecular Medicine (M.K., L.R., B.T., C.L.), Clinical Neuroscience (S.G.), Woman and Child Health (M.K., M.H.), and Pathology (A.H.) Karolinska Hospital, S-171 76 Stockholm, Sweden; and Laboratory for Cancer Genetics (O.-P.K.), Institute of Medical Technology, University of Tampere and Tampere University Hospital, FIN-33521 Tampere, Finland

Address all correspondence and requests for reprints to: Dr. Magnus Kjellman, Department of Surgery, Karolinska Hospital P9:03, S-171 76 Stockholm, Sweden. E-mail: kmak{at}kir.ks.se

To identify chromosomal regions that may contain loci for tumor suppressor genes involved in adrenocortical tumor development, a panel of 60 tumors (39 carcinomas and 21 adenomas) were screened for loss of heterozygosity. Although the vast majority of loss of heterozygosity (LOH) were detected in the carcinomas and involved chromosomes 2, 4, 11, and 18, only few were found in the adenomas. Therefore, 2 loci that harbor the familial cancer syndromes Carney complex in 2p16 and the multiple endocrine neoplasia type 1 gene in 11q13 were further studied in 27 (13 carcinomas and 14 adenomas) of the 60 tumors. Detailed analysis of the 2p16 region mapped a minimal area of overlapping deletions to a 1-centimorgan region, which is separate from the Carney complex locus. LOH for a microsatellite marker (PYGM), very close to the MEN1 gene, was detected in all 8 informative carcinomas (100%) and in 2 of 14 adenomas. Of the 27 cases analyzed in detail, 13 cases (11 carcinomas and 2 adenomas) showed LOH on chromosome 11 and was therefore selected for MEN1 gene mutation analysis. In 6 cases a common polymorphism (Asp⁴¹⁸Asp) was found, but no mutation was detected. In conclusion, our data indicate the existence of tumor suppressor genes at multiple chromosomal locations, whose inactivations are involved in the development of adrenocortical carcinomas. Loss of genetic material from 2p16 was strongly associated with the malignant phenotype, as it was seen in almost all carcinomas but not in any of the adenomas. LOH in 11q13 also occurred frequently in the carcinomas, but was not associated with a MEN1 mutation, suggesting the involvement of a different tumor suppressor gene on this chromosome.

This article has been cited by other articles:

				M Volante, C Buttigliero, E Greco, A Berruti, and M Papotti Pathological and molecular features of adrenocortical carcinoma: an update J. Clin. Pathol., July 1, 2008; 61(7): 787 - 793. [Abstract] [Full Text] [PDF]

				P. S. H. Soon, K. L. McDonald, B. G. Robinson, and S. B. Sidhu Molecular Markers and the Pathogenesis of Adrenocortical Cancer Oncologist, May 1, 2008; 13(5): 548 - 561. [Abstract] [Full Text] [PDF]

				R. Libe, A. Fratticci, and J. Bertherat Adrenocortical cancer: pathophysiology and clinical management Endocr. Relat. Cancer, March 1, 2007; 14(1): 13 - 28. [Abstract] [Full Text] [PDF]

				I. Bourdeau, L. Matyakhina, S. G. Stergiopoulos, F. Sandrini, S. Boikos, and C. A. Stratakis 17q22-24 Chromosomal Losses and Alterations of Protein Kinase A Subunit Expression and Activity in Adrenocorticotropin-Independent Macronodular Adrenal Hyperplasia J. Clin. Endocrinol. Metab., September 1, 2006; 91(9): 3626 - 3632. [Abstract] [Full Text] [PDF]

				R. Libe and J. Bertherat Molecular genetics of adrenocortical tumours, from familial to sporadic diseases Eur. J. Endocrinol., October 1, 2005; 153(4): 477 - 487. [Abstract] [Full Text] [PDF]

				J. Bertherat, L. Groussin, F. Sandrini, L. Matyakhina, T. Bei, S. Stergiopoulos, T. Papageorgiou, I. Bourdeau, L. S. Kirschner, C. Vincent-Dejean, et al. Molecular and Functional Analysis of PRKAR1A and its Locus (17q22-24) in Sporadic Adrenocortical Tumors: 17q Losses, Somatic Mutations, and Protein Kinase A Expression and Activity Cancer Res., September 1, 2003; 63(17): 5308 - 5319. [Abstract] [Full Text] [PDF]

				M.-H. Bernard, S. Sidhu, N. Berger, J.-L. Peix, D. J. Marsh, B. G. Robinson, V. Gaston, Y. Le Bouc, and C. Gicquel A Case Report in Favor of a Multistep Adrenocortical Tumorigenesis J. Clin. Endocrinol. Metab., March 1, 2003; 88(3): 998 - 1001. [Abstract] [Full Text] [PDF]

				C. A. Koch, K. Pacak, and G. P. Chrousos The Molecular Pathogenesis of Hereditary and Sporadic Adrenocortical and Adrenomedullary Tumors J. Clin. Endocrinol. Metab., December 1, 2002; 87(12): 5367 - 5384. [Abstract] [Full Text] [PDF]

				A. Peri, P. Luciani, B. Conforti, S. Baglioni-Peri, F. Cioppi, C. Crescioli, P. Ferruzzi, S. Gelmini, G. Arnaldi, G. Nesi, et al. Variable Expression of the Transcription Factors cAMP Response Element-Binding Protein and Inducible cAMP Early Repressor in the Normal Adrenal Cortex and in Adrenocortical Adenomas and Carcinomas J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5443 - 5449. [Abstract] [Full Text] [PDF]

				C. Gicquel, X. Bertagna, V. Gaston, J. Coste, A. Louvel, E. Baudin, J. Bertherat, Y. Chapuis, J.-M. Duclos, M. Schlumberger, et al. Molecular Markers and Long-Term Recurrences in a Large Cohort of Patients with Sporadic Adrenocortical Tumors Cancer Res., September 1, 2001; 61(18): 6762 - 6767. [Abstract] [Full Text] [PDF]

				C. A STRATAKIS, S. E TAYMANS, D. SCHTEINGART, and B. R HADDAD Segmental uniparental isodisomy (UPD) for 2p16 without clinical symptoms: implications for UPD and other genetic studies of chromosome 2 J. Med. Genet., February 1, 2001; 38(2): 106 - 109. [Full Text]

				M. A. Godil, M. P. Atlas, R. I. Parker, C. J. Priebe, M. M. Zerah, P. Kane, J. Tsung, and T. A. Wilson Metastatic Congenital Adrenocortical Carcinoma: A Case Report with Tumor Remission at 31/2 Years J. Clin. Endocrinol. Metab., November 1, 2000; 85(11): 3964 - 3967. [Abstract] [Full Text]

				K.-M. Schulte, M. Mengel, M. Heinze, D. Simon, S. Scheuring, K. Köhrer, and H.-D. Röher Complete Sequencing and Messenger Ribonucleic Acid Expression Analysis of the MEN I Gene in Adrenal Cancer J. Clin. Endocrinol. Metab., January 1, 2000; 85(1): 441 - 448. [Abstract] [Full Text]