Molecular Genetics of Colorectal Cancer

Abstract

Over the past three decades, molecular genetic studies have revealed some critical mutations underlying the pathogenesis of the sporadic and inherited forms of colorectal cancer (CRC). A relatively limited number of oncogenes and tumor-suppressor genes-most prominently the APC, KRAS, and p53 genes-are mutated in a sizeable fraction of CRCs, and a larger collection of genes that are mutated in subsets of CRC have begun to be defined. Together with DNA-methylation and chromatin-structure changes, the mutations act to dysregulate conserved signaling networks that exert context-dependent effects on critical cell phenotypes, including the regulation of cellular metabolism, proliferation, differentiation, and survival. Much work remains to be done to fully understand the nature and significance of the individual and collective genetic and epigenetic defects in CRC. Some key concepts for the field have emerged, two of which are emphasized in this review. Specifically, the gene defects in CRC often target proteins and pathways that exert pleiotropic effects on the cancer cell phenotype, and particular genetic and epigenetic alterations are linked to biologically and clinically distinct subsets of CRC.

ER stress transcription factor Xbp1 suppresses intestinal tumorigenesis and directs intestinal stem cells

“…§, P = 0.1024; *, P < 0.05; **, P < 0.01; ***, P < 0.001. e.g., inactivating somatic mutations in adenomatous polyposis coli (APC) are very common and appear early as a rate-limiting step in CRC pathogenesis (Kinzler and Vogelstein, 1996;Fearon, 2011;Cancer Genome Atlas Network, 2012) but late in CAC (Leedham et al, 2009). Germline mutations in APC also cause familial adenomatous polyposis.…”

Phytochemical Investigations of Three Rhodocodon (Hyacinthaceae Sensu APG II) Species

“…However, it must be borne in mind that aspirin is not a selective COX-2 inhibitor 16 and so for future studies a comparison of these and other homoisoflavanoids against a more appropriate inhibitor such as the NSAID celecoxib, which is considered by some to be clinically relevant in the treatment of colorectal cancer, is required. 16,42 The effect of these compounds on CRC cells in vitro should not be limited to COX-2, as the development and progression of colorectal cancer occurs via several molecular mechanisms, [43][44][45][46] and so future studies will be needed to further investigate and characterize the effect of these compounds on the growth of HCA-7, and other types of colorectal cancer cells to gain greater insight into their therapeutic potential.…”

High expression of Fatty Acid‐Binding Protein 5 promotes cell growth and metastatic potential of colorectal cancer cells

“…Genetic mutations, epigenetic alterations, inflammation, and environmental factors such as diet are thought to be linked to CRC initiation and progression 2, 3. Despite growing clinical significance, the detailed molecular mechanisms underlying metastasis in CRC remain poorly understood.…”