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 Sidhu, S. Articles by Robinson, B. G. Search for Related Content PubMed PubMed Citation Articles by Sidhu, S. Articles by Robinson, B. G.

Comparative Genomic Hybridization Analysis of Adrenocortical Tumors

Cancer Genetics, Kolling Institute of Medical Research (S.S., D.J.M., G.T., B.G.R.), and Departments of Surgery (S.S., C.P.B., L.D.) and Pathology (J.P.), Royal North Shore Hospital, St. Leonards, New South Wales 2065, Australia; Departments of Molecular Medicine (S.S., D.J.M., G.T., B.G.R.), Pathology (J.P.), Medicine (B.G.R.), and Surgery (L.D.), University of Sydney, New South Wales 2006, Australia; Department of Surgery, Liverpool Hospital (P.C.), Liverpool, New South Wales 2170, Australia; Department of Surgery, St. George Hospital (C.J.M.), Kogarah, New South Wales 2217, Australia; Department of Surgery, Ward 37, Royal Victoria Hospital (C.F.J.R.), Belfast, United Kingdom BT12 6BA; and Department of General and Trauma Surgery, Heinrich Heine University (K.-M.S., H.-D.R.), Düsseldorf, Germany

Address all correspondence and requests for reprints to: Prof. Bruce G. Robinson, Cancer Genetics, Kolling Institute of Medical Research, Royal North Shore Hospital, St. Leonards, New South Wales 2065, Australia. E-mail: . bgr{at}med.usyd.edu.au

Abstract

Comparative genomic hybridization (CGH) is a molecular cytogenetic technique that allows the entire genome of a tumor to be surveyed for gains and losses of DNA copy sequences. A limited number of studies reporting the use of this technique in adult adrenocortical tumors have yielded conflicting results.

In this study we performed CGH analysis on 13 malignant, 18 benign, and 1 tumor of indeterminate malignant potential with the aim of identifying genetic loci consistently implicated in the development and progression of adrenocortical tumors. Tissue samples from 32 patients with histologically proven adrenocortical tumors were available for CGH analysis. CGH changes were seen in all cancers, 11 of 18 (61%) adenomas, and the 1 tumor of indeterminate malignant potential. Of the adrenal cancers, the most common gains were seen on chromosomes 5 (46%), 12 (38%), 19 (31%), and 4 (31%). Losses were most frequently seen at 1p (62%), 17p (54%), 22 (38%), 2q (31%), and 11q (31%). Of the benign adenomas, the most common change was gain of 4q (22%).

Mann-Whitney analysis showed a highly significant difference between the cancer group (mean changes, 7.6) and the adenoma group (mean changes, 1.1) for the number of observed CGH changes (P < 0.01). Logistic regression analysis showed that the number of CGH changes was highly predictive of tumor type (P < 0.01).

This study has identified several chromosomal loci implicated in adrenocortical tumorigenesis. Activation of a protooncogene(s) on chromosome 4 may be an early event, with progression from adenoma to carcinoma involving activation of oncogenes on chromosomes 5 and 12 and inactivation of tumor suppressor genes on chromosome arms 1p and 17p.

This article has been cited by other articles:

				M. Bielinska, H. Parviainen, S. Kiiveri, M. Heikinheimo, and D. B. Wilson REVIEW PAPER: Origin and Molecular Pathology of Adrenocortical Neoplasms Vet. Pathol., March 1, 2009; 46(2): 194 - 210. [Abstract] [Full Text] [PDF]

				T. J. Giordano, R. Kuick, T. Else, P. G. Gauger, M. Vinco, J. Bauersfeld, D. Sanders, D. G. Thomas, G. Doherty, and G. Hammer Molecular Classification and Prognostication of Adrenocortical Tumors by Transcriptome Profiling Clin. Cancer Res., January 15, 2009; 15(2): 668 - 676. [Abstract] [Full Text] [PDF]

				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]

				E. A. Stephan, T.-H. Chung, C. S. Grant, S. Kim, D. D. Von Hoff, J. M. Trent, and M. J. Demeure Adrenocortical carcinoma survival rates correlated to genomic copy number variants Mol. Cancer Ther., February 1, 2008; 7(2): 425 - 431. [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]

				R. Libe, L. Groussin, F. Tissier, C. Elie, F. Rene-Corail, A. Fratticci, E. Jullian, P. Beck-Peccoz, X. Bertagna, C. Gicquel, et al. Somatic TP53 Mutations Are Relatively Rare among Adrenocortical Cancers with the Frequent 17p13 Loss of Heterozygosity Clin. Cancer Res., February 1, 2007; 13(3): 844 - 850. [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]

				A. Horvath, L. Mathyakina, Q. Vong, V. Baxendale, A. L. Y. Pang, W.-Y. Chan, and C. A. Stratakis Serial Analysis of Gene Expression in Adrenocortical Hyperplasia Caused by a Germline PRKAR1A Mutation J. Clin. Endocrinol. Metab., February 1, 2006; 91(2): 584 - 596. [Abstract] [Full Text] [PDF]

				L. S. Kirschner Emerging Treatment Strategies for Adrenocortical Carcinoma: A New Hope J. Clin. Endocrinol. Metab., January 1, 2006; 91(1): 14 - 21. [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]

				E. M Pinto, A. E. C. Billerbeck, M. C. B. V. Fragoso, B. B. Mendonca, and A. C. Latronico Deletion Mapping of Chromosome 17 in Benign and Malignant Adrenocortical Tumors Associated with the Arg337His Mutation of the p53 Tumor Suppressor Protein J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2976 - 2981. [Abstract] [Full Text] [PDF]

				F. de Fraipont, M. El Atifi, N. Cherradi, G. Le Moigne, G. Defaye, R. Houlgatte, J. Bertherat, X. Bertagna, P.-F. Plouin, E. Baudin, et al. Gene Expression Profiling of Human Adrenocortical Tumors Using Complementary Deoxyribonucleic Acid Microarrays Identifies Several Candidate Genes as Markers of Malignancy J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1819 - 1829. [Abstract] [Full Text] [PDF]

				C A Longui, S H V Lemos-Marini, B Figueiredo, B B Mendonca, M Castro, R Liberatore Jr, C Watanabe, C L P Lancellotti, M N Rocha, M B Melo, et al. Inhibin {alpha}-subunit (INHA) gene and locus changes in paediatric adrenocortical tumours from TP53 R337H mutation heterozygote carriers J. Med. Genet., May 1, 2004; 41(5): 354 - 359. [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]