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Neoplasia-associated Chromosome Translocations Resulting in Gene Truncation
Ioannis Panagopoulos1, Sverre Heim2,3
1Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; ioannis.panagopoulos@rr-research.no.
Abstract:
Chromosomal translocations in cancer as well as benign neoplasias typically lead to the formation of fusion genes. Such genes may encode chimeric proteins when two protein-coding regions fuse in-frame, or they may result in deregulation of genes via promoter swapping or translocation of the gene into the vicinity of a highly active regulatory element. A less studied consequence of chromosomal translocations is the fusion of two breakpoint genes resulting in an out-of-frame chimera. The breaks then occur in one or both protein-coding regions forming a stop codon in the chimeric transcript shortly after the fusion point. Though the latter genetic events and mechanisms at first awoke little research interest, careful investigations have established them as neither rare nor inconsequential. In the present work, we review and discuss the truncation of genes in neoplastic cells resulting from chromosomal rearrangements, especially from seemingly balanced translocations.
Insights
Chromosomal translocations can create fusion genes, leading to chimeric proteins or gene deregulation in cancers. This review focuses on out-of-frame gene fusions and truncations resulting from chromosomal rearrangements.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Chromosomal translocations are common in neoplasias, often forming fusion genes.
- Fusion genes can arise from in-frame coding region fusion, promoter swapping, or regulatory element proximity.
- Out-of-frame chimeras, a less-studied consequence, result from breaks within coding regions, leading to premature stop codons.
Purpose of the Study:
- To review and discuss gene truncation events in neoplastic cells.
- To highlight the significance of out-of-frame chimeras arising from chromosomal rearrangements.
- To emphasize the role of seemingly balanced translocations in gene truncation.
Main Methods:
- Literature review of chromosomal rearrangements and their consequences.
- Analysis of genetic events leading to gene truncation in cancer.
- Discussion of mechanisms involving out-of-frame fusion and promoter swapping.
Main Results:
- Chromosomal translocations frequently lead to fusion genes, impacting cancer development.
- Out-of-frame chimeras, though less studied, are significant genetic events in neoplasia.
- Gene truncation due to chromosomal rearrangements, including balanced translocations, is a notable consequence.
Conclusions:
- Gene truncation resulting from chromosomal rearrangements is a critical, though often overlooked, mechanism in cancer.
- Understanding out-of-frame chimeras provides deeper insights into oncogenesis.
- Further research into these genetic alterations is crucial for comprehending and potentially targeting neoplastic diseases.
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