#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

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


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


Sources

1. eco.iarc.fr [homepage on the Internet]. WHO, International Agency for Research on Cancer; [updated 2012 Jul 26;cited 2015 jun 15]. Available from: http:/ / www.eco.iarc.fr/ eucan.

2. nczisk.sk [internetová stránka]. Národné centrum zdravotníckych informácií, Slovenská republika; [aktualizované 31. decembra 2008; citované 15. júna 2015]. Dostupné z: hhtp:/ / www.nczisk.sk.

3. Fearon ER, Vogelstein B. A genetic model for colonal tumorigenesis. Cell 1990; 61(5): 759– 767.

4. Takayama T, Ohi M, Hayashi T et al. Analysis of K‑ ras, APC, and beta‑catenin in aber­rant crypt foci in sporadic adenoma, cancer, and familial adenomatous polyposis. Gastroenterology 2001; 121(3): 599– 611.

5. Zauber AG, Winawer SJ, O’Brien MJ et al. Colonoscopic polypectomy and long term prevention of colorectal cancer deaths. N Engl J Med 2012; 366(8): 687– 696. doi: 10.1056/ NEJMoa1100370.

6. Bienz M, Clevers H. Link­ing colorectal cancer to Wnt signaling. Cell 2000; 103(2): 311– 320.

7. Rus­so A, Bazan V, Iacopetta B et al. The TP53 colorectal cancer international col­laborative study on the prognostic and predictive significance of the p53 mutation. J Clin Oncol 2005; 23(30): 7518– 7528.

8. Morán A, Ortega P, de Juan C et al. Dif­ferential colorectal carcinogenesis: molecular basis and clinical relevance. World J Gastrointest Oncol 2010; 2(3): 151– 158. doi: 10.4251/ wjgo.v2.i3.151.

9. Boland CR, Thibodeau SN, Hamilton SR et al. A National Cancer Institute Workshop on Microsatel­lite Instability for cancer detection and familial predisposition: developement of international crieteria for the determination of microsatelite instability in colorectal cancer. Cancer Res 1988; 58(22): 5248– 5257.

10. Křepelová A, Pavlíková K, Plevová P. Dia­gnostika Lynchova syndromu –  nové geny a metody. Klin Onkol 2006; 19 (Suppl): S76– S81.

11. Whitehall VL, Wals MD, Zoung J et al. Methylation of O‑ 6- methylguanine DNA methyltransferase characterises a subset of colorectal cancer with low‑ level DNA microsatel­lite instability. Cancer Res 2001; 61(3): 827– 830.

12. Palomaki GE, McClain MR, Melilo S et al. EGAPP sup­plementary evidence rewiew: DNA test­ing strategies aimed at reduc­ing morbidity and mortality from Lynch syndrome. Genet Med 2009; 11(1): 42– 65. doi: 10.1097/ GIM.0b013e31818fa2db.

13. Kempers MJ, Kuiper RP, Ockeloen CW et al. Risk of colorectal and endometrial cancer in EPCAM deletion‑ positive Lynch syndrome: a cohort study. Lancet Oncol 2011; 12(1): 49– 55. doi: 10.1016/ S1470‑ 2045(10)70265‑ 5.

14. Weis­sman SM, Bel­lcross C, Bitter CC et al. Genetic counsel­ing considerations in the evaluation of familie for Lynch syndrome –  a review. J Genet Couns 2011; 20(1): 5– 19. doi: 10.1007/ s10897‑ 010‑ 9325‑ x.

15. Goodenberg M, Lindor NM. Lynch syndrome and MYH‑as­sociated polyposis: review and test­ing strategy. J Clin Gastroenterol 2011; 45(6): 488– 500. doi: 10.1097/ MCG.0b013e318206489c.

16. Guarinos C, Sánchez‑ Fortún C, Rodríguez‑ Soler M et al. Ser­rated polyposis syndrome: molecular, pathological and clinical aspects. World J Gastroenterol 2012; 18(20): 2452– 2461. doi: 10.3748/ wjg.v18.i20.2452.

17. Guarinos C, Sánchez‑ Fortún C, Rodriguez‑ Soler M et al. Clinical subtypes and molecular characteristics of ser­rated polyposis syndrome. Clin Gastroenterol Hepatol 2013; 11(6): 705– 711. doi: 10.1016/ j.cgh.2012.12.045.

18. Leggett B, Whitehall V. Role of ser­raded pathway in colorectal cancer pathogenesis. Gastroenterology 2010; 138(6): 2088– 2100. doi: 10.1053/ j.gastro.2009.12.066.

19. Rex DK, Ahnen DJ, Baron JA et al. Ser­rated lesions of colorectum: review and recom­mendations from an expert panel. Amer J Gastroenterol 2012; 107(9): 1315– 1329. doi: 10.1038/ 

Labels
Paediatric clinical oncology Surgery Clinical oncology

Article was published in

Clinical Oncology

Issue Supplementum 1

2016 Issue Supplementum 1

Most read in this issue
Topics Journals
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#