Title | Analysis and Interpretation of the Impact of Missense Variants in Cancer. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Petrosino M, Novak L, Pasquo A, Chiaraluce R, Turina P, Capriotti E, Consalvi V |
Journal | Int J Mol Sci |
Volume | 22 |
Issue | 11 |
Date Published | 2021 May 21 |
ISSN | 1422-0067 |
Keywords | Computational Biology, Computer Simulation, Humans, Mutation, Missense, Neoplasms, Protein Stability, Proteins |
Abstract | Large scale genome sequencing allowed the identification of a massive number of genetic variations, whose impact on human health is still unknown. In this review we analyze, by an in silico-based strategy, the impact of missense variants on cancer-related genes, whose effect on protein stability and function was experimentally determined. We collected a set of 164 variants from 11 proteins to analyze the impact of missense mutations at structural and functional levels, and to assess the performance of state-of-the-art methods (FoldX and Meta-SNP) for predicting protein stability change and pathogenicity. The result of our analysis shows that a combination of experimental data on protein stability and in silico pathogenicity predictions allowed the identification of a subset of variants with a high probability of having a deleterious phenotypic effect, as confirmed by the significant enrichment of the subset in variants annotated in the COSMIC database as putative cancer-driving variants. Our analysis suggests that the integration of experimental and computational approaches may contribute to evaluate the risk for complex disorders and develop more effective treatment strategies. |
DOI | 10.3390/ijms22115416 |
Alternate Journal | Int J Mol Sci |
PubMed ID | 34063805 |
PubMed Central ID | PMC8196604 |