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Unbalanced translocation, a major chromosome alteration causing loss of heterozygosity in human lung cancer

Abstract

Loss of heterozygosity (LOH) is a major genetic event causing inactivation of tumor suppressor genes in human carcinogenesis. To elucidate chromosomal mechanisms causing LOH, 201 LOHs in 10 cases of human lung cancer, which were detected by a genome-wide single nucleotide polymorphism array analysis, were investigated for responsible chromosome alterations by integrating information on breakpoints for DNA copy number changes obtained by array-comparative genome hybridization and on numerical and structural chromosomal alterations obtained by spectral karyotyping. The majority (80%) of LOHs were partial chromosome LOHs caused by structural chromosomal alterations, while the remaining (20%) were whole chromosome LOHs caused by whole chromosome deletions. Unbalanced translocation was defined as the most frequent alteration, and it accounted for 30% of all LOHs. Three other structural alterations—interstitial deletion (19%), mitotic recombination (9%) and gene conversion (6%)—also contributed to the occurrence of LOH, while terminal deletion contributed to only a small subset (1%). Since unbalanced translocation is a common chromosomal alteration in lung cancer cells, the results in the present study strongly indicate that a considerable fraction of LOHs detected in lung cancer cells are caused by unbalanced translocation.

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Acknowledgements

This work was supported by Grants-in-Aid from the Ministry of Health, Labor and Welfare of Japan for the 3rd-term Comprehensive 10-year Strategy for Cancer Control and for Cancer Research (16-1 and 19-9), and from the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NiBio). We thank Kaho Minoura and Yayoi Fukuoka of Agilent Technologies Japan for technical assistance in array-CGH analysis.

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Correspondence to J Yokota.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Ogiwara, H., Kohno, T., Nakanishi, H. et al. Unbalanced translocation, a major chromosome alteration causing loss of heterozygosity in human lung cancer. Oncogene 27, 4788–4797 (2008). https://doi.org/10.1038/onc.2008.113

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