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Cancer type-specific alterations in actin genes: Worth a closer look?
Christophe Ampe1, Laura Witjes1, Marleen Van Troys1
1Department of Biomolecular Medicine, Ghent University, Gent, Belgium.
Abstract:
Actins form a strongly conserved family of proteins that are central to the functioning of the actin cytoskeleton partaking in natural processes such as cell division, adhesion, contraction and migration. These processes, however, also occur during the various phases of cancer progression. Yet, surprisingly, alterations in the six human actin genes in cancer studies have received little attention and the focus was mostly on deregulated expression levels of actins and even more so of actin-binding or regulatory proteins. Starting from the early mutation work in the 1980s, we propose based on reviewing literature and data from patient cancer genomes that alterations in actin genes are different in distinct cancer subtypes, suggesting some specificity. These actin gene alterations include (missense) mutations, gene fusions and copy number alterations (deletions and amplifications) and we illustrate their occurrence for a limited number of examples including actin mutations in lymphoid cancers and nonmelanoma skin cancer and actin gene copy number alterations for breast, prostate and liver cancers. A challenge in the future will be to further sort out the specificity per actin gene, alteration type and cancer subtype. Even more challenging is (experimentally) distinguishing between cause and consequence: which alterations are passengers and which are involved in tumor progression of particular cancer subtypes?
Insights
Alterations in human actin genes, including mutations and copy number changes, show cancer-specific patterns. Further research is needed to distinguish driver mutations from passenger events in tumor progression.
Area of Science:
- Molecular Biology
- Cancer Genetics
- Cell Biology
Background:
- Actins are essential proteins for cytoskeleton functions like cell division, adhesion, contraction, and migration.
- These cellular processes are also critical during cancer progression.
- Despite their importance, actin gene alterations have been understudied in cancer, with research focusing more on expression levels of actin-related proteins.
Purpose of the Study:
- To investigate the role and specificity of alterations in human actin genes across different cancer subtypes.
- To review and analyze existing literature and patient cancer genome data regarding actin gene mutations, fusions, and copy number alterations.
Main Methods:
- Literature review of actin gene alterations in cancer.
- Analysis of patient cancer genome data.
- Case examples illustrating actin gene mutations and copy number alterations in specific cancers.
Main Results:
- Actin gene alterations (missense mutations, gene fusions, copy number variations) exhibit distinct patterns across various cancer subtypes.
- Examples include actin mutations in lymphoid and nonmelanoma skin cancers, and copy number alterations in breast, prostate, and liver cancers.
Conclusions:
- Actin gene alterations are not random and suggest a degree of cancer-type specificity.
- Future challenges include elucidating the specific roles of each actin gene and alteration type in distinct cancer subtypes.
- Distinguishing between causative and consequential (passenger) alterations in tumor progression remains a significant hurdle.
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