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Chromosome instability in human lung cancers: possible underlying mechanisms and potential consequences in the pathogenesis

Oncogene volume 21, pages 6884–6897 (2002)Cite this article

Abstract

Chromosomal abnormality is one of the hallmarks of neoplastic cells, and the persistent presence of chromosome instability (CIN) has been demonstrated in human cancers, including lung cancer. Recent progress in molecular and cellular biology as well as cytogenetics has shed light on the underlying mechanisms and the biological and clinical significance of chromosome abnormalities and the CIN phenotype. Chromosome abnormalities can be classified broadly into numerical (i.e., aneuploidy) and structural alterations (e.g., deletion, translocation, homogenously staining region (HSR), double minutes (DMs)). However, both alterations usually occur in the same cells, suggesting some overlap in their underlying mechanisms. Missegregation of chromosomes may result from various causes, including defects of mitotic spindle checkpoint, abnormal centrosome formation and failure of cytokinesis, while structural alterations of chromosomes may be caused especially by failure in the repair of DNA double-strand breaks (DSBs) due to the impairment of DNA damage checkpoints and/or DSB repair systems. Recent studies also suggest that telomere erosion may be involved. The consequential acquisition of the CIN phenotype would give lung cancer cells an excellent opportunity to efficiently alter their characteristics so as to be more malignant and suitable to their microenvironment, thereby gaining a selective growth advantage.

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Acknowledgements

We apologize for the omission of many important original papers because of limited space. We are grateful to all members of our division for helpful discussion and comments on the manuscript as well as to surgical pathologists, clinicians and surgeons of our lung cancer research group of the Aichi Cancer Center for continuing fruitful collaborations for many years.

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  1. Division of Molecular Oncology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan

    Akira Masuda & Takashi Takahashi

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  1. Akira Masuda
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  2. Takashi Takahashi
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Correspondence to Takashi Takahashi.

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Masuda, A., Takahashi, T. Chromosome instability in human lung cancers: possible underlying mechanisms and potential consequences in the pathogenesis. Oncogene 21, 6884–6897 (2002). https://doi.org/10.1038/sj.onc.1205566

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