The mystery of chromosomal translocations in cancer
1Department of Pathology, Montefiore Medical Center, Bronx, NY, USA. lkoss@montefiore.org
Abstract:
Chromosomal translocations in human cancer may result in products that can be suppressed by targeting drugs. An example is bcr-abl tyrosine kinase in chronic myelogenous leukemia that can be treated with imatinib mesylate. However, the mechanisms of translocations or exchanges of chromosomal segments are virtually unknown. In this summary, chromosomal translocations in human cancer are compared with 'crossing over' of chromosomal segments occurring during the first meiotic division. Several proposed mechanisms of the exchange of DNA between and among chromosomes are discussed. The conditions that appear essential for these events to occur are listed. Among them are proximity of the involved DNA segments, mechanisms of excising the target DNA, its transport to the new location, and integration into the pre-existing chromosome. The conclusion based on extensive review of the literature is that practically nothing is known about the mechanism of 'crossing over' or translocation. Based on prior work on normal human cells, it is suggested that only one of the two autosomes participates in these events that may include loss of heterozygozity, another common abnormality in human cancer.
Insights
Chromosomal translocations in cancer are poorly understood. This review compares them to meiotic crossing over, suggesting DNA proximity and excision/integration mechanisms are key, yet the precise process remains largely unknown.
Area of Science:
- Genetics
- Molecular Biology
- Oncology
Background:
- Chromosomal translocations are hallmarks of human cancers.
- Targeting drug therapies, like imatinib mesylate for chronic myelogenous leukemia (CML) via bcr-abl tyrosine kinase, demonstrate the clinical relevance of translocation products.
- However, the underlying mechanisms driving these chromosomal rearrangements are largely unknown.
Purpose of the Study:
- To compare chromosomal translocations in human cancer with meiotic crossing over.
- To discuss proposed mechanisms for DNA exchange between and among chromosomes.
- To identify essential conditions for translocation events.
Main Methods:
- Literature review and comparison of chromosomal translocations in cancer with meiotic crossing over.
- Discussion of proposed DNA exchange mechanisms.
- Listing of conditions essential for translocation events.
Main Results:
- Chromosomal translocations share similarities with meiotic crossing over.
- Essential conditions for translocations include proximity of DNA segments, DNA excision, transport, and integration.
- The precise molecular mechanisms of both crossing over and translocations remain largely unknown.
Conclusions:
- The mechanisms of chromosomal translocations and meiotic crossing over are not well understood.
- Proposed translocation mechanisms involve DNA proximity, excision, transport, and integration.
- It is hypothesized that only one autosome participates in these events, potentially leading to loss of heterozygosity in cancer.
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