This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Stark, M. Articles by Hayward, N. Search for Related Content PubMed PubMed Citation Articles by Stark, M. Articles by Hayward, N.

Genome-Wide Loss of Heterozygosity and Copy Number Analysis in Melanoma Using High-Density Single-Nucleotide Polymorphism Arrays

Oncogenomics Laboratory, Queensland Institute of Medical Research, Herston, Queensland, Australia

Requests for reprints: Nicholas Hayward, Oncogenomics Laboratory, Queensland Institute of Medical Research, 300 Herston Road, Herston, Brisbane, QLD 4006, Australia. Phone: 61-7-33620306; Fax: 61-7-38453508; E-mail: Nick.Hayward{at}qimr.edu.au.

Although a number of genes related to melanoma development have been identified through candidate gene screening approaches, few studies have attempted to conduct such analyses on a genome-wide scale. Here we use Illumina 317K whole-genome single-nucleotide polymorphism arrays to define a comprehensive allelotype of melanoma based on loss of heterozygosity (LOH) and copy number changes in a panel of 76 melanoma cell lines. In keeping with previous reports, we found frequent LOH on chromosome arms 9p (72%), 10p (55%), 10q (55%), 9q (49%), 6q (43%), 11q (43%), and 17p (41%). Tumor suppressor genes (TSGs) can be identified through homozygous deletion (HD). We detected 174 HDs, the most common of which targeted CDKN2A (n = 33). The second highest frequency of HD occurred in PTEN (n = 8), another well known melanoma TSG. HDs were also common for PTPRD (n = 7) and HDAC4 (n = 3), TSGs recently found to be mutated or deleted in other cancer types. Analysis of other HDs and regions of LOH that we have identified might lead to the characterization of further melanoma TSGs. We noted 197 regional amplifications, including some centered on the melanoma oncogenes MITF (n = 9), NRAS (n = 3), BRAF (n = 3), and CCND1 (n = 3). Other amplifications potentially target novel oncogenes important in the development of a subset of melanomas. The numerous focal amplifications and HDs we have documented here are the first step toward identifying a comprehensive catalog of genes involved in melanoma development, some of which may be useful prognostic markers or targets for therapies to treat this disease. [Cancer Res 2007;67(6):2632–42]

This article has been cited by other articles:

				B. Modrek, L. Ge, A. Pandita, E. Lin, S. Mohan, P. Yue, S. Guerrero, W. M. Lin, T. Pham, Z. Modrusan, et al. Oncogenic Activating Mutations Are Associated with Local Copy Gain Mol. Cancer Res., August 1, 2009; 7(8): 1244 - 1252. [Abstract] [Full Text] [PDF]

				A. V. Antonov, S. Dietmann, P. Wong, D. Lutter, and H. W. Mewes GeneSet2miRNA: finding the signature of cooperative miRNA activities in the gene lists Nucleic Acids Res., July 1, 2009; 37(suppl_2): W323 - W328. [Abstract] [Full Text] [PDF]

				R. Marone, D. Erhart, A. C. Mertz, T. Bohnacker, C. Schnell, V. Cmiljanovic, F. Stauffer, C. Garcia-Echeverria, B. Giese, S.-M. Maira, et al. Targeting Melanoma with Dual Phosphoinositide 3-Kinase/Mammalian Target of Rapamycin Inhibitors Mol. Cancer Res., April 1, 2009; 7(4): 601 - 613. [Abstract] [Full Text] [PDF]

				H. Zheng, L. Gao, Y. Feng, L. Yuan, H. Zhao, and L. A. Cornelius Down-regulation of Rap1GAP via Promoter Hypermethylation Promotes Melanoma Cell Proliferation, Survival, and Migration Cancer Res., January 15, 2009; 69(2): 449 - 457. [Abstract] [Full Text] [PDF]

				D. A. Solomon, J.-S. Kim, J. C. Cronin, Z. Sibenaller, T. Ryken, S. A. Rosenberg, H. Ressom, W. Jean, D. Bigner, H. Yan, et al. Mutational Inactivation of PTPRD in Glioblastoma Multiforme and Malignant Melanoma Cancer Res., December 15, 2008; 68(24): 10300 - 10306. [Abstract] [Full Text] [PDF]

				R. J. Leary, J. C. Lin, J. Cummins, S. Boca, L. D. Wood, D. W. Parsons, S. Jones, T. Sjoblom, B.-H. Park, R. Parsons, et al. Integrated analysis of homozygous deletions, focal amplifications, and sequence alterations in breast and colorectal cancers PNAS, October 21, 2008; 105(42): 16224 - 16229. [Abstract] [Full Text] [PDF]

				A. Sekulic, P. Haluska Jr, A. J. Miller, J. G. De Lamo, S. Ejadi, J. S. Pulido, D. R. Salomao, E. C. Thorland, R. G. Vile, D. L. Swanson, et al. Malignant Melanoma in the 21st Century: The Emerging Molecular Landscape Mayo Clin. Proc., July 1, 2008; 83(7): 825 - 846. [Abstract] [Full Text] [PDF]

				S. R. Moore, D. L. Persons, J. A. Sosman, D. Bobadilla, V. Bedell, D. D. Smith, S. R. Wolman, R. J. Tuthill, J. Moon, V. K. Sondak, et al. Detection of Copy Number Alterations in Metastatic Melanoma by a DNA Fluorescence In situ Hybridization Probe Panel and Array Comparative Genomic Hybridization: A Southwest Oncology Group Study (S9431) Clin. Cancer Res., May 15, 2008; 14(10): 2927 - 2935. [Abstract] [Full Text] [PDF]

				W. Maat, S. H. W. Beiboer, M. J. Jager, G. P. M. Luyten, N. A. Gruis, and P. A. van der Velden Epigenetic Regulation Identifies RASEF as a Tumor-Suppressor Gene in Uveal Melanoma Invest. Ophthalmol. Vis. Sci., April 1, 2008; 49(4): 1291 - 1298. [Abstract] [Full Text] [PDF]

				W. M. Lin, A. C. Baker, R. Beroukhim, W. Winckler, W. Feng, J. M. Marmion, E. Laine, H. Greulich, H. Tseng, C. Gates, et al. Modeling Genomic Diversity and Tumor Dependency in Malignant Melanoma Cancer Res., February 1, 2008; 68(3): 664 - 673. [Abstract] [Full Text] [PDF]

				V. Vallacchi, M. Daniotti, F. Ratti, D. Di Stasi, P. Deho, A. De Filippo, G. Tragni, A. Balsari, A. Carbone, L. Rivoltini, et al. CCN3/Nephroblastoma Overexpressed Matricellular Protein Regulates Integrin Expression, Adhesion, and Dissemination in Melanoma Cancer Res., February 1, 2008; 68(3): 715 - 723. [Abstract] [Full Text] [PDF]

				G. Paroni, N. Cernotta, C. Dello Russo, P. Gallinari, M. Pallaoro, C. Foti, F. Talamo, L. Orsatti, C. Steinkuhler, and C. Brancolini PP2A Regulates HDAC4 Nuclear Import Mol. Biol. Cell, February 1, 2008; 19(2): 655 - 667. [Abstract] [Full Text] [PDF]