title: Differential colorectal carcinogenesis: Molecular basis and clinical relevance.
abstract: Colorectal cancer (CCR) is one of the most frequent cancers in developed countries. It poses a major public health problem and there is renewed interest in understanding the basic principles of the molecular biology of colorectal cancer. It has been established that sporadic CCRs can arise from at least two different carcinogenic pathways. The traditional pathway, also called the suppressor or chromosomal instability pathway, follows the Fearon and Vogelstein model and shows mutation in classical oncogenes and tumour suppressor genes, such as K-ras, adenomatous polyposis coli, deleted in colorectal cancer, or p53. Alterations in the Wnt pathway are also very common in this type of tumour. The second main colorectal carcinogenesis pathway is the mutator pathway. This pathway is present in nearly 15% of all cases of sporadic colorectal cancer. It is characterized by the presence of mutations in the microsatellite sequences caused by a defect in the DNA mismatch repair genes, mostly in hMLH1 or hMSH2. These two pathways have clear molecular differences, which will be reviewed in this article, but they also present distinct histopathological features. More strikingly, their clinical behaviours are completely different, having the "mutator" tumours a better outcome than the "suppressor" tumours.
authors.affiliation: Alberto Morán, Paloma Ortega, Carmen de Juan, Tamara Fernández-Marcelo, Cristina Frías, Pilar Iniesta, Manuel Benito, the second Department of Biochemistry and Molecular Biology, School of Pharmacy, Complutense University, 28040-Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Morán
authors.forename: Paloma
authors.initials: P
authors.lastname: Ortega
authors.forename: Carmen
authors.initials: C
authors.lastname: de Juan
authors.forename: Tamara
authors.initials: T
authors.lastname: Fernández-Marcelo
authors.forename: Cristina
authors.initials: C
authors.lastname: Frías
authors.forename: Andrés
authors.initials: A
authors.lastname: Sánchez-Pernaute
authors.forename: Antonio José
authors.initials: AJ
authors.lastname: Torres
authors.forename: Eduardo
authors.initials: E
authors.lastname: Díaz-Rubio
authors.forename: Pilar
authors.initials: P
authors.lastname: Iniesta
authors.forename: Manuel
authors.initials: M
authors.lastname: Benito