Genetics of colorectal polyps

Abstract

Currently, genetic investigation of human tumours starts from the analysis of advanced cancers. Once a given genetic alteration has been found in advanced tumours, this same alteration is investigated in the pre-neoplastic lesions. The aim of this approach is to assess the significance of the genetic alteration during the carcinogenic process. This review is focused on alterations that have proven to be present in pre-neoplastic lesions that are associated to colorectal cancer (ACF and early adenoma). Alterations that are present at the early stages are likely to play a crucial role in colorectal tumorigenesis. Colorectal tumorigenesis is extremely heterogeneous from a genetic point of view: tumours follow alternative molecular pathways and show different phenotypes (CIN, MIN and CIMP). Tumours are genetically heterogeneous from their early stages: the sequence of genetic events that accumulate within cells during progression to malignancy appears to be determined by the first events. These events have been investigated in ACF and in early adenomas. The understanding of the molecular mechanisms underlying genesis and progression of colorectal tumours will allow the development of new tools for cancer prevention and early diagnosis, as well as for therapeutic approaches specific for different molecular targets.