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Identification of Specific Gene Copy Number Changes in Asbestos-Related Lung Cancer

¹ Department of Pathology, Haartman Institute, University of Helsinki and Helsinki University Central Hospital Diagnostics Laboratory, Helsinki University Central Hospital; ² Departments of Occupational Medicine, Epidemiology, and Toxicology and Industrial Hygiene, Finnish Institute of Occupational Health; ³ Laboratory of Computer and Information Science, Helsinki University of Technology, Helsinki, Finland and ⁴ Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Requests for reprints: Penny Nymark, Finnish Institute of Occupational Health, Topeliuksenkatu 41aA, 00250 Helsinki, Finland. Phone: 358-3-04742210; Fax: 358-3-04742021; E-mail: penny.nymark{at}helsinki.fi.

Asbestos is a well-known lung cancer-causing mineral fiber. In vitro and in vivo experiments have shown that asbestos can cause chromosomal damage and aberrations. Lung tumors, in general, have several recurrently amplified and deleted chromosomal regions. To investigate whether a distinct chromosomal aberration profile could be detected in the lung tumors of heavily asbestos-exposed patients, we analyzed the copy number profiles of 14 lung tumors from highly asbestos-exposed patients and 14 matched tumors from nonexposed patients using classic comparative genomic hybridization (CGH). A specific profile could lead to identification of the underlying genes that may act as mediators of tumor formation and progression. In addition, array CGH analyses on cDNA microarrays (13,000 clones) were carried out on 20 of the same patients. Classic CGH showed, on average, more aberrations in asbestos-exposed than in nonexposed patients, and an altered region in chromosome 2 seemed to occur more frequently in the asbestos-exposed patients. Array CGH revealed aberrations in 18 regions that were significantly associated with either of the two groups. The most significant regions were 2p21-p16.3, 5q35.3, 9q33.3-q34.11, 9q34.13-q34.3, 11p15.5, 14q11.2, and 19p13.1-p13.3 (P < 0.005). Furthermore, 11 fragile sites coincided with the 18 asbestos-associated regions (P = 0.08), which may imply preferentially caused DNA damage at these sites. Our findings are the first evidence, indicating that asbestos exposure may produce a specific DNA damage profile. (Cancer Res 2006; 66(11): 5737-43)

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