TITLE

Genomic instability and colon carcinogenesis: from the perspective of genes

AUTHOR(S)
Rao, Chinthalapally V.; Yamada, Hiroshi Y.
PUB. DATE
May 2013
SOURCE
Frontiers in Oncology;May2013, Vol. 3, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
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 andWD repeat domain containing 7, transforming growth factor-b, chro-mosome 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.
ACCESSION #
88067178

 

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