Genetics of Colorectal Tumorigenesis (Possibilities of Testing and Screening Prediction of Hereditary Form of Colorectal Cancer – Lynch Syndrome)

Czech version

Authors: I. Mľkvá
Authors‘ workplace: Oddelenie klinickej genetiky, Ústav lekárskej biológie, genetiky a klinickej genetiky LF UK a UN Bratislava, Slovenská republika
Published in: Klin Onkol 2016; 29(Supplementum 1): 55-61
Category: Review
doi: https://doi.org/10.14735/amko2016S55

Overview

Colorectal cancer is currently one of the most frequent cancers in developed countries. Understanding the molecular principles of its pathogenesis has recently come into focus of many oncogenetic studies. Colorectal cancer also represents an ideal model for the study of molecular basis of cancerogenesis owing to the wide availability of its precursor lesions and the existence of several notorious genetic predispositions such as familial adenomatous polyposis and Lynch syndrome. The classical model of colorectal tumorigenesis, described by Fearon and Vogelstein, suggested the idea of a conventional progression from adenoma to carcinoma. It was based on a careful analysis of mutations occurring within particular stages of carcinogenesis with regards to their stepwise accumulations leading to neoplastic transformation of the colonic epithelium. Recently, new evidence has pointed to an alternative model of colorectal tumorigenesis introducing the concept of serrated precursors. This alternative pathway, known as the serrated pathway, has provided a new perspective on colorectal cancer development. Nowadays, three molecular pathways leading to colorectal tumorigenesis are recognized: 1. the chromosomal instability pathway typified by familial adenomatous polyposis; 2. the mutator pathway characterized by inactivation of DNA mismatch repair genes such as in Lynch syndrome or a number of sporadic colorectal cancers; 3. the hypermethylation serrated neoplasia pathway characterized by excessive methylation of some CpG islands in the promoter region of certain genes (positive CpG islands methylator phenotype) (CIMP+).

Key words:
colorectal cancer – colorectal tumorigenesis – Lynch syndrome – microsatellite instability – hypermethylation phenotype

The author declares she has no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Submitted:
14. 7. 2016

Accepted:
8. 9. 2016

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