Mechanisms and impacts of chromosomal translocations in cancers

Abstract

Chromosomal aberrations have been associated with cancer development since their discovery more than a hundred years ago. Chromosomal translocations, a type of particular structural changes involving heterologous chromosomes, have made a critical impact on diagnosis, prognosis and treatment of cancers. For example, the discovery of translocation between chromosomes 9 and 22 and the subsequent success of targeting the fusion product BCR-ABL transformed the therapy for chronic myelogenous leukemia. In the past few decades, tremendous progress has been achieved towards elucidating the mechanism causing chromosomal translocations. This review focuses on the basic mechanisms underlying the generation of chromosomal translocations. In particular, the contribution of frequency of DNA double strand breaks and spatial proximity of translocating loci is discussed.

Keywords

DNA double strand breaks / chromosomal translocations / genomic instability / spatial proximity / carcinogenesis

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Acknowledgements

I thank Drs. Yu Zhang, Monica Gostissa, Zhangguo Chen, and Shan Zha for comments. I apologize to those whose work was not cited due to length restrictions. This work was supported by University of Colorado School of Medicine start-up fund, Leukemia Research Foundation, and Boettcher Foundation for J.H.W. J.H.W. is a recipient of Boettcher Foundation Webb-Waring Biomedical Research Award. The author declares no conflict of interest.

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