title: Focus on genetic and epigenetic events of colorectal cancer pathogenesis: implications for molecular diagnosis.
abstract: Originally, colorectal cancer (CRC) tumorigenesis was understood as a multistep process that involved accumulation of tumor suppressor genes and oncogenes mutations, such as APC, TP53 and KRAS. However, this assumption proposed a relatively limited repertoire of genetic alterations. In the last decade, there have been major advances in knowledge of multiple molecular pathways involved in CRC pathogenesis, particularly regarding cytogenetic and epigenetic events. Microsatellite instability, chromosomal instability and CpG island methylator phenotype are the most analyzed cytogenetic changes, while DNA methylation, modifications in histone proteins and microRNAs (miRNAs) were analyzed in the field of epigenetic alterations. Therefore, CRC development results from interactions at many levels between genetic and epigenetic amendments. Furthermore, hereditary cancer syndrome and individual or environmental risk factors should not be ignored. The difficulties in this setting are addressed to understand the molecular basis of individual susceptibility to CRC and to determine the roles of genetic and epigenetic alterations, in order to yield more effective prevention strategies in CRC patients and directing their treatment. This review summarizes the most investigated biomolecular pathways involved in CRC pathogenesis, their role as biomarkers for early CRC diagnosis and their possible use to stratify susceptible patients into appropriate screening or surveillance programs.
authors: Oncology Unit 2, Azienda Ospedaliera-Universitaria Pisana, Ospedale Santa Chiara, Pisa, 56126, Italy, federica.z@libero.it.
authors: Federica
authors: F
authors: Zoratto
authors: Luigi
authors: L
authors: Rossi
authors: Monica
authors: M
authors: Verrico
authors: Anselmo
authors: A
authors: Papa
authors: Enrico
authors: E
authors: Basso
authors: Angelo
authors: A
authors: Zullo
authors: Luigi
authors: L
authors: Tomao
authors: Adriana
authors: A
authors: Romiti
authors: Giuseppe
authors: G
authors: Lo Russo
authors: Silverio
authors: S
authors: Tomao
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D043171:Chromosomal Instability / Q000235:genetics; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D057089:Pathology, Molecular
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs