A critical re-examination of the role of chromosome translocations in cancer
AbstractA chromosome translocation occurs at random in many hematological and solid malignancies and is considered the initiating event of carcinogenesis. However, the early events of carcinogenesis do not entirely align with this hypothesis. First, chromosome translocations are observed more frequently than expected if they were truly a random event. Second, chromosome translocations are often found in healthy individuals, and a specific rearrangement may be observed in up to half of the general population. Third, tissue proliferation is observed before chromosome translocation. Further, the at-random breakage–re-ligation–selection mechanism proposed to explain chromosome translocations in cancer is not well understood, particularly regarding how chromosomes come in contact with each other. These observations open the possibility that an alternative mechanism may contribute. Here, a model is proposed to describe how chromosome translocations, which are often observed in stressed tissue, could be produced in relation to transcription. Transcription–associated recombination may explain how over-expressed genes that are temporally in close proximity may become abnormally fused. This model offers a framework for the hypothesis that early carcinogenesis promotes chromosome translocation, rather than that cancer is initiated by chromosome translocation. Further, the hypothesis suggests that the role of genetic modifications observed early in malignancy is more complex and less determining than currently considered and implies that therapy targeting genetic modifications could miss the causal mechanism.
How to Cite
Satgé, D. (2017). A critical re-examination of the role of chromosome translocations in cancer. Organisms. Journal of Biological Sciences, 1(1), 53–60. https://doi.org/10.13133/2532-5876/13877
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