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Human Molecular Genetics, 2003, Vol. 12, No. 7 791-801
DOI: 10.1093/hmg/ddg083
© 2003 Oxford University Press

A comprehensive search for DNA amplification in lung cancer identifies inhibitors of apoptosis cIAP1 and cIAP2 as candidate oncogenes

Zunyan Dai1,2, Wei-Guo Zhu3, Carl D. Morrison1,2, Romulo M. Brena1,6, Dominic J. Smiraglia1, Aparna Raval1, Yue-Zhong Wu1, Laura J. Rush1,4, Patrick Ross5, Julian R. Molina7, Gregory A. Otterson3 and Christoph Plass1,*

1Program of Human Cancer Genetics, Department of Molecular Virology, Immunology and Medical Genetics, 2Department of Pathology, 3Division of Hematology/Oncology, Department of Internal Medicine, 4Department of Veterinary Biosciences, 5Department of Clinical Surgery, 6Department of Molecular Genetics and the Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA and 7Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA

Received November 15, 2002; Accepted February 1, 2003

Amplification of oncogenes is an important mechanism that can cause gene overexpression and contributes to tumor development. The identification of amplified regions might have both prognostic and therapeutic significance. We used primary lung carcinomas and lung cancer cell lines for restriction landmark genomic scanning (RLGS) to identify novel amplified sequences. Enhanced RLGS fragments that indicate gene amplification were observed in primary tumors and lung cancer cell lines of both non-small cell lung cancer and small cell lung cancer. We identified one novel amplicon on chromosome 11q22, in addition to previously reported amplicons that include oncogenes MYCC, MYCL1 and previously identified amplification of chromosomal regions 6q21 and 3q26–27. Amplification of 11q22 has been reported in other types of cancer and was refined to an ~1.19 Mbp region for which the complete sequence is available. Based on a patient sample with a small region of low-level amplification we were able to further narrow this region to 0.92 Mbp. Genes localized in this region include two inhibitors of apoptosis (cIAP1 and cIAP2). Immunohistochemistry and western blot analysis identified cIAP1 and cIAP2 as potential oncogenes in this region as both are overexpressed in multiple lung cancers with or without higher copy numbers.

* To whom correspondence should be addressed at: The Ohio State University, Division of Human Cancer Genetics, Medical Research Facility 464A, 420 West 12th Ave., Columbus, OH 43210, USA. Tel: +1 6142926505; Fax: +1 6146884761; Email: plass-1{at}medctr.osu.edu


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