title: Genetic alterations in colorectal cancer.
abstract: Colorectal cancer (CRC) is the third most common cancer in men and the second most common cancer in women worldwide. Both genetic and epigenetic alterations are common in CRC and are the driving force of tumorigenesis. The adenoma-carcinoma sequence was proposed in the 1980s that described transformation of normal colorectal epithelium to an adenoma and ultimately to an invasive and metastatic tumor. Initial genetic changes start in an early adenoma and accumulate as it transforms to carcinoma. Chromosomal instability, microsatellite instability and CpG island methylator phenotype pathways are responsible for genetic instability in colorectal cancer. Chromosomal instability pathway consist of activation of proto-oncogenes (KRAS) and inactivation of at least three tumor suppression genes, namely loss of APC, p53 and loss of heterozogosity (LOH) of long arm of chromosome 18. Mutations of TGFBR and PIK3CA genes have also been recently described. Herein we briefly discuss the basic concepts of genetic integrity and the consequences of defects in the DNA repair relevant to CRC. Epigenetic alterations, essential in CRC tumorigenesis, are also reviewed alongside clinical information relevant to CRC.
authors.affiliation: Louisiana State University Health Shreveport, LA.
authors.forename: Tannaz
authors.initials: T
authors.lastname: Armaghany
authors.forename: Jon D
authors.initials: JD
authors.lastname: Wilson
authors.forename: Quyen
authors.initials: Q
authors.lastname: Chu
authors.forename: Glenn
authors.initials: G
authors.lastname: Mills