Comprehensive Analysis of Human Colorectal Cancers Harboring Polymerase Epsilon Mutations
Abstract
1. Introduction
2. Results and Discussion
2.1. POLe Mutation Spectrum in Human Cancers
2.2. POLe-Associated Mutations in Colorectal Cancers
2.3. Colorectal Cancer Differential Gene Expression Patterns in POLe Mutant Samples
2.4. Evidence of POLe-Specific Mutation Signatures from In Vivo Mutagenic Screens and Experiments
3. Materials and Methods
3.1. Data Accession and Processing
3.2. Determination of Mutation Driver Potential
3.3. TCGA Expression
3.4. Pan-Cancer Analysis of POLe Mutations
3.5. Protein Structure Analysis
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Protein | Mutation | Tertiary Structure Interaction Changes | Electrostatic Surface Potential Changes | ΔΔG Value (kcal/mol) |
---|---|---|---|---|
PIK3CA | R88Q | Yes, decreased | Neutral to negative | −4.53 |
E545K | Yes, decreased | Negative to neutral | +0.08 | |
H1074R | No | Negative to partial negative | −0.56 | |
CNOT | R559Q | Yes, increased | No change | −0.08 |
FBXW7 | R465Q | No | No change | −1.83 |
R465H | No | No change | −1.40 | |
R465C | No | No change | +7.88 | |
CTNNB1 | S45F | No | No change | −1.87 |
SF3B1 | R196Q | No | Positive to negative | −0.23 |
R315Q | No | Positive to neutral | +0.54 | |
CHD4 | R1338I | No | No change | −2.31 |
CHD8 | R546C | No | Positive to partial positive | −0.37 |
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Gibson, L.M.; Konda, P.; Bliss, H.J.; Nelakurti, D.D.; Mirzaei, G.; Bouley, R.A.; Wang, J.J.; Petreaca, R.C. Comprehensive Analysis of Human Colorectal Cancers Harboring Polymerase Epsilon Mutations. Int. J. Mol. Sci. 2025, 26, 7208. https://doi.org/10.3390/ijms26157208
Gibson LM, Konda P, Bliss HJ, Nelakurti DD, Mirzaei G, Bouley RA, Wang JJ, Petreaca RC. Comprehensive Analysis of Human Colorectal Cancers Harboring Polymerase Epsilon Mutations. International Journal of Molecular Sciences. 2025; 26(15):7208. https://doi.org/10.3390/ijms26157208
Chicago/Turabian StyleGibson, Louis M., Phanithan Konda, Hunter J. Bliss, Devi D. Nelakurti, Golrokh Mirzaei, Renee A. Bouley, Jing J. Wang, and Ruben C. Petreaca. 2025. "Comprehensive Analysis of Human Colorectal Cancers Harboring Polymerase Epsilon Mutations" International Journal of Molecular Sciences 26, no. 15: 7208. https://doi.org/10.3390/ijms26157208
APA StyleGibson, L. M., Konda, P., Bliss, H. J., Nelakurti, D. D., Mirzaei, G., Bouley, R. A., Wang, J. J., & Petreaca, R. C. (2025). Comprehensive Analysis of Human Colorectal Cancers Harboring Polymerase Epsilon Mutations. International Journal of Molecular Sciences, 26(15), 7208. https://doi.org/10.3390/ijms26157208