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Research Articles: Therapeutics, Targets, and Development

Adrenocortical carcinoma survival rates correlated to genomic copy number variants

¹ Genetic Basis of Human Disease Division, ² Computational Biology Division, and ³ Clinical Translational Research Division, Translational Genomics Research Institute, Phoenix, Arizona; ⁴ Department of Surgery, Mayo Clinic, Rochester, Minnesota; ⁵ School of Computing and Informatics, Ira Fulton School of Engineering, Arizona State University, Tempe, Arizona; and ⁶ Department of Surgery, University of Arizona, Tucson, Arizona

Requests for reprints: Elizabeth A. Stephan, Genetic Basis of Human Disease Division, Translational Genomics Research Institute, 445 North 5th Street, Phoenix, AZ 85004. Phone: 602-343-8817; Fax: 602-343-8840. E-mail: estephan{at}tgen.org

Abstract

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy accounting for between 0.02% and 0.2% of all cancer deaths. Surgical removal offers the only current potential for cure. Unfortunately, ACC has undergone metastatic spread in 40% to 70% of patients at the time of diagnosis. Standard chemotherapy with mitotane is often ineffective with intolerable side effects. The modern molecular technology of comparative genomic hybridization allows the examination of DNA for chromosomal alterations, which can lend biological insight into cancer processes. Genomes of 25 ACC clinical samples were queried on the Agilent 44K Human Genome comparative genomic hybridization array detecting regions of chromosomal gain and loss within the tumor population. Commonly shared amplifications appearing in 50% of tumors at P 10^–4 include regions within chromosomes 5, 7, 12, 16q, and 20. Deleted genomic regions within ACC include portions of chromosomes 1, 3p, 10q, 11, 14q, 15q, 17, and 22q. Genomic aberrations in regions associated with differential survival (P 0.05) and presence in 20% of tumors include amplifications of 6q, 7q, 12q, and 19p. Deletions within stratified survival groups include localized regions within 3, 8, 10p, 16q, 17q, and 19q. Statistical analysis of this genetic landscape reveals a set of chromosomal aberrations strongly associated with survival in an accumulation-dependent fashion. These regions may hold prognostic indicators and offer therapeutic targets that can be used to develop novel treatments for aggressive tumors. [Mol Cancer Ther 2008;7(2):425–31]

Grant support: Advancing Treatments for Adrenocortical Carcinoma Fund.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Note: Array CGH data have been deposited in Gene Expression Omnibus (accession no. GSE7482).

E.A. Stephan and T-H. Chung contributed equally to this work.

⁷ Supplementary material for this article is available at Molecular Cancer Therapeutics Online (http://mct.aacrjournals.org/).

Received 4/11/07; revised 10/ 9/07; accepted 12/31/07.