Genomic and Epigenetic Instability in Colorectal Cancer Pathogenesis

By W. Grady, J. Carethers. Gastroenterology, 2008

949 citations recorded by the source corpus.

Colorectal cancer arises as a consequence of the accumulation of genetic alterations (gene mutations, gene amplification, and so on) and epigenetic alterations (aberrant DNA methylation, chromatin modifications, and so on) that transform colonic epithelial cells into colon adenocarcinoma cells. The loss of genomic stability and resulting gene alterations are key molecular pathogenic steps that occur early in tumorigenesis; they permit the acquisition of a sufficient number of alterations in tumor suppressor genes and oncogenes that transform cells and promote tumor progression. Two predominant forms of genomic instability that have been identified in colon cancer are microsatellite instability and chromosome instability. Substantial progress has been made to identify causes of chromosomal instability in colorectal cells and to determine the effects of the different forms of genomic instability on the biological and clinical behavior of colon tumors. In addition to genomic instability, epigenetic instability results in the aberrant methylation of tumor suppressor genes. Determining the causes and roles of genomic and epigenomic instability in colon tumor formation has the potential to yield more effective prevention strategies and therapeutics for patients with colorectal cancer.

Subfields: Cancer Research, Molecular Biology, Pathology and Forensic Medicine

View Paper: https://www.semanticscholar.org/paper/a273b3b26d619d8fe6844956dc5fb3379c49f33e

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Citations in the corpus

• Colorectal carcinoma: Pathologic aspects. (2012, background): “In particular, promoter hypermethylation of the MLH1, one of the MMR genes, is demonstrated in the majority of sporadic colorectal cancers with a MSI phenotype (108,111,112).”
• Colorectal Carcinoma: A General Overview and Future Perspectives in Colorectal Cancer (2017, background): “The CIN pathway, which is also considered to be the classical pathway since it represents the cause of up to 80%–85% of all CRC cases [26], is characterized by imbalances in the number of chromosomes, thus leading to aneuploydic tumours and loss of heterozygosity (LOH).”
• Global colorectal cancer burden in 2020 and projections to 2040 (2021, background): “the consequent carcinogenesis, comprises three major aberrant events: microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and chromosomal instability (CIN) [26].”
• Escherichia coli induces DNA damage in vivo and triggers genomic instability in mammalian cells (2010, background): “Sporadic colorectal cancer essentially is a genetic disease in which chromosomal instability, found in 85% of cases, is central to the tumorigenesis process (20, 21).”