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Mathematical modeling the order of driver gene mutations in colorectal cancer

Tumor heterogeneity is a large obstacle for cancer study and treatment. Different cancer patients may involve different combinations of gene mutations or the distinct regulatory pathways for inducing the progression of tumor. Investigating the pathways of gene mutations which can cause the formation...

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Autores principales: Li, Lingling, Hu, Yulu, Xu, Yunshan, Tang, Sanyi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10332632/
https://www.ncbi.nlm.nih.gov/pubmed/37368936
http://dx.doi.org/10.1371/journal.pcbi.1011225
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author Li, Lingling
Hu, Yulu
Xu, Yunshan
Tang, Sanyi
author_facet Li, Lingling
Hu, Yulu
Xu, Yunshan
Tang, Sanyi
author_sort Li, Lingling
collection PubMed
description Tumor heterogeneity is a large obstacle for cancer study and treatment. Different cancer patients may involve different combinations of gene mutations or the distinct regulatory pathways for inducing the progression of tumor. Investigating the pathways of gene mutations which can cause the formation of tumor can provide a basis for the personalized treatment of cancer. Studies suggested that KRAS, APC and TP53 are the most significant driver genes for colorectal cancer. However, it is still an open issue regarding the detailed mutation order of these genes in the development of colorectal cancer. For this purpose, we analyze the mathematical model considering all orders of mutations in oncogene, KRAS and tumor suppressor genes, APC and TP53, and fit it on data describing the incidence rates of colorectal cancer at different age from the Surveillance Epidemiology and End Results registry in the United States for the year 1973–2013. The specific orders that can induce the development of colorectal cancer are identified by the model fitting. The fitting results indicate that the mutation orders with KRAS → APC → TP53, APC → TP53 → KRAS and APC → KRAS → TP53 explain the age–specific risk of colorectal cancer with very well. Furthermore, eleven pathways of gene mutations can be accepted for the mutation order of genes with KRAS → APC → TP53, APC → TP53 → KRAS and APC → KRAS → TP53, and the alternation of APC acts as the initiating or promoting event in the colorectal cancer. The estimated mutation rates of cells in the different pathways demonstrate that genetic instability must exist in colorectal cancer with alterations of genes, KRAS, APC and TP53.
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spelling pubmed-103326322023-07-11 Mathematical modeling the order of driver gene mutations in colorectal cancer Li, Lingling Hu, Yulu Xu, Yunshan Tang, Sanyi PLoS Comput Biol Research Article Tumor heterogeneity is a large obstacle for cancer study and treatment. Different cancer patients may involve different combinations of gene mutations or the distinct regulatory pathways for inducing the progression of tumor. Investigating the pathways of gene mutations which can cause the formation of tumor can provide a basis for the personalized treatment of cancer. Studies suggested that KRAS, APC and TP53 are the most significant driver genes for colorectal cancer. However, it is still an open issue regarding the detailed mutation order of these genes in the development of colorectal cancer. For this purpose, we analyze the mathematical model considering all orders of mutations in oncogene, KRAS and tumor suppressor genes, APC and TP53, and fit it on data describing the incidence rates of colorectal cancer at different age from the Surveillance Epidemiology and End Results registry in the United States for the year 1973–2013. The specific orders that can induce the development of colorectal cancer are identified by the model fitting. The fitting results indicate that the mutation orders with KRAS → APC → TP53, APC → TP53 → KRAS and APC → KRAS → TP53 explain the age–specific risk of colorectal cancer with very well. Furthermore, eleven pathways of gene mutations can be accepted for the mutation order of genes with KRAS → APC → TP53, APC → TP53 → KRAS and APC → KRAS → TP53, and the alternation of APC acts as the initiating or promoting event in the colorectal cancer. The estimated mutation rates of cells in the different pathways demonstrate that genetic instability must exist in colorectal cancer with alterations of genes, KRAS, APC and TP53. Public Library of Science 2023-06-27 /pmc/articles/PMC10332632/ /pubmed/37368936 http://dx.doi.org/10.1371/journal.pcbi.1011225 Text en © 2023 Li et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Li, Lingling
Hu, Yulu
Xu, Yunshan
Tang, Sanyi
Mathematical modeling the order of driver gene mutations in colorectal cancer
title Mathematical modeling the order of driver gene mutations in colorectal cancer
title_full Mathematical modeling the order of driver gene mutations in colorectal cancer
title_fullStr Mathematical modeling the order of driver gene mutations in colorectal cancer
title_full_unstemmed Mathematical modeling the order of driver gene mutations in colorectal cancer
title_short Mathematical modeling the order of driver gene mutations in colorectal cancer
title_sort mathematical modeling the order of driver gene mutations in colorectal cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10332632/
https://www.ncbi.nlm.nih.gov/pubmed/37368936
http://dx.doi.org/10.1371/journal.pcbi.1011225
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