Detection of driver mutations and genomic signatures in endometrial cancers using artificial intelligence algorithms.

Autor: Stan A; Biology Program, The Ohio State University, Marion, Ohio, United States of America., Bosart K; Biology Program, The Ohio State University, Marion, Ohio, United States of America., Kaur M; Biology Program, The Ohio State University, Marion, Ohio, United States of America., Vo M; Biology Department, Xavier University, Cincinnati, Ohio, United States of America., Escorcia W; Biology Department, Xavier University, Cincinnati, Ohio, United States of America., Yoder RJ; Department of Chemistry and Biochemistry, The Ohio State University, Marion, Ohio, United States of America., Bouley RA; Department of Chemistry and Biochemistry, The Ohio State University, Marion, Ohio, United States of America., Petreaca RC; Department of Molecular Genetics, The Ohio State University, Marion, Ohio, United States of America.; James Comprehensive Cancer Center, The Ohio State University Columbus, Columbus, Ohio, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 Feb 26; Vol. 19 (2), pp. e0299114. Date of Electronic Publication: 2024 Feb 26 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0299114
Abstrakt: Analyzed endometrial cancer (EC) genomes have allowed for the identification of molecular signatures, which enable the classification, and sometimes prognostication, of these cancers. Artificial intelligence algorithms have facilitated the partitioning of mutations into driver and passenger based on a variety of parameters, including gene function and frequency of mutation. Here, we undertook an evaluation of EC cancer genomes deposited on the Catalogue of Somatic Mutations in Cancers (COSMIC), with the goal to classify all mutations as either driver or passenger. Our analysis showed that approximately 2.5% of all mutations are driver and cause cellular transformation and immortalization. We also characterized nucleotide level mutation signatures, gross chromosomal re-arrangements, and gene expression profiles. We observed that endometrial cancers show distinct nucleotide substitution and chromosomal re-arrangement signatures compared to other cancers. We also identified high expression levels of the CLDN18 claudin gene, which is involved in growth, survival, metastasis and proliferation. We then used in silico protein structure analysis to examine the effect of certain previously uncharacterized driver mutations on protein structure. We found that certain mutations in CTNNB1 and TP53 increase protein stability, which may contribute to cellular transformation. While our analysis retrieved previously classified mutations and genomic alterations, which is to be expected, this study also identified new signatures. Additionally, we show that artificial intelligence algorithms can be effectively leveraged to accurately predict key drivers of cancer. This analysis will expand our understanding of ECs and improve the molecular toolbox for classification, diagnosis, or potential treatment of these cancers.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Stan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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