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Genomic Instability and Colon Carcinogenesis: From the Perspective of Genes

Colon cancer is the second most lethal cancer; approximately 600,000 people die of it annually in the world. Colon carcinogenesis generally follows a slow and stepwise process of accumulation of mutations under the influence of environmental and epigenetic factors. To adopt a personalized (tailored)...

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Autores principales: Rao, Chinthalapally V., Yamada, Hiroshi Y.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659308/
https://www.ncbi.nlm.nih.gov/pubmed/23734346
http://dx.doi.org/10.3389/fonc.2013.00130
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author Rao, Chinthalapally V.
Yamada, Hiroshi Y.
author_facet Rao, Chinthalapally V.
Yamada, Hiroshi Y.
author_sort Rao, Chinthalapally V.
collection PubMed
description Colon cancer is the second most lethal cancer; approximately 600,000 people die of it annually in the world. Colon carcinogenesis generally follows a slow and stepwise process of accumulation of mutations under the influence of environmental and epigenetic factors. To adopt a personalized (tailored) cancer therapy approach and to improve current strategies for prevention, diagnosis, prognosis, and therapy overall, advanced understanding of molecular events associated with colon carcinogenesis is necessary. A contemporary approach that combines genetics, epigenomics, and signaling pathways has revealed many genetic/genomic alterations associated with colon cancer progression and their relationships to a genomic instability phenotype prevalent in colon cancer. In this review, we describe the relationship between gene mutations associated with colon carcinogenesis and a genomic instability phenotype, and we discuss possible clinical applications of genomic instability studies. Colon carcinogenesis is associated with frequent mutations in several pathways that include phosphatidylinositol 3-kinase, adenomatous polyposis coli, p53 (TP53), F-box and WD repeat domain containing 7, transforming growth factor-β, chromosome cohesion, and K-RAS. These genes frequently mutated in pathways affecting colon cancer were designated colon cancer (CAN) genes. Aberrations in major colon CAN genes have a causal relationship to genomic instability. Conversely, genomic instability itself plays a role in colon carcinogenesis in experimental settings, as demonstrated in transgenic mouse models with high genomic instability. Thus, there is a feedback-type relationship between CAN gene mutations and genomic instability. These genetic/genomic studies have led to emerging efforts to apply the knowledge to colon cancer prognosis and to targeted therapy.
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spelling pubmed-36593082013-06-03 Genomic Instability and Colon Carcinogenesis: From the Perspective of Genes Rao, Chinthalapally V. Yamada, Hiroshi Y. Front Oncol Oncology Colon cancer is the second most lethal cancer; approximately 600,000 people die of it annually in the world. Colon carcinogenesis generally follows a slow and stepwise process of accumulation of mutations under the influence of environmental and epigenetic factors. To adopt a personalized (tailored) cancer therapy approach and to improve current strategies for prevention, diagnosis, prognosis, and therapy overall, advanced understanding of molecular events associated with colon carcinogenesis is necessary. A contemporary approach that combines genetics, epigenomics, and signaling pathways has revealed many genetic/genomic alterations associated with colon cancer progression and their relationships to a genomic instability phenotype prevalent in colon cancer. In this review, we describe the relationship between gene mutations associated with colon carcinogenesis and a genomic instability phenotype, and we discuss possible clinical applications of genomic instability studies. Colon carcinogenesis is associated with frequent mutations in several pathways that include phosphatidylinositol 3-kinase, adenomatous polyposis coli, p53 (TP53), F-box and WD repeat domain containing 7, transforming growth factor-β, chromosome cohesion, and K-RAS. These genes frequently mutated in pathways affecting colon cancer were designated colon cancer (CAN) genes. Aberrations in major colon CAN genes have a causal relationship to genomic instability. Conversely, genomic instability itself plays a role in colon carcinogenesis in experimental settings, as demonstrated in transgenic mouse models with high genomic instability. Thus, there is a feedback-type relationship between CAN gene mutations and genomic instability. These genetic/genomic studies have led to emerging efforts to apply the knowledge to colon cancer prognosis and to targeted therapy. Frontiers Media S.A. 2013-05-21 /pmc/articles/PMC3659308/ /pubmed/23734346 http://dx.doi.org/10.3389/fonc.2013.00130 Text en Copyright © 2013 Rao and Yamada. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
spellingShingle Oncology
Rao, Chinthalapally V.
Yamada, Hiroshi Y.
Genomic Instability and Colon Carcinogenesis: From the Perspective of Genes
title Genomic Instability and Colon Carcinogenesis: From the Perspective of Genes
title_full Genomic Instability and Colon Carcinogenesis: From the Perspective of Genes
title_fullStr Genomic Instability and Colon Carcinogenesis: From the Perspective of Genes
title_full_unstemmed Genomic Instability and Colon Carcinogenesis: From the Perspective of Genes
title_short Genomic Instability and Colon Carcinogenesis: From the Perspective of Genes
title_sort genomic instability and colon carcinogenesis: from the perspective of genes
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659308/
https://www.ncbi.nlm.nih.gov/pubmed/23734346
http://dx.doi.org/10.3389/fonc.2013.00130
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