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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front Med    2012, Vol. 6 Issue (3) : 263-274    https://doi.org/10.1007/s11684-012-0215-5
REVIEW
Mechanisms and impacts of chromosomal translocations in cancers
Jing H. Wang()
Integrated Department of Immunology, University of Colorado School of Medicine and National Jewish Health, Denver, CO 80206, USA
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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     
Corresponding Author(s): Wang Jing H.,Email:jing.wang@ucdenver.edu   
Issue Date: 05 September 2012
 Cite this article:   
Jing H. Wang. Mechanisms and impacts of chromosomal translocations in cancers[J]. Front Med, 2012, 6(3): 263-274.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-012-0215-5
https://academic.hep.com.cn/fmd/EN/Y2012/V6/I3/263
Fig.1  Overview of V(D)J recombination and CSR in B cells. Germline configuration of locus (top) is shown with V (variable) (red box), D (diversity) (gray box) and J (joining) (blue box) gene segments located upstream and a set of constant region exons (black oval) located downstream. Grey diamond: intronic enhancer (iEμ) and Igh 3′ regulatory region (Igh3′RR). Black and white triangles flanking the V, D, J gene segments: recombination signal sequences (RSSs). V(D)J recombination is initiated by RAGs which recognize RSSs and completed by NHEJ. The rearranged locus (middle) is shown with V(D)J exon assembled. White and color boxes: switch (S) regions. The upstream donor Sμ (yellow box) and downstream acceptor Sγ1 (green box), as an example, are indicated for CSR. CSR is catalyzed by AID and NHEJ. The switched locus (bottom) is shown with the hybrid Sμ/Sγ1 sequence and the Cγ1 exons juxtaposed next to assembled V(D)J exon.
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