DNA methylation as an epigenetic biomarker in colorectal cancer

Silva,Tiago   Donizetti; Vidigal,Veronica   Marques; Felipe,Aledson  Vitor; De Lima,Jacqueline   Miranda; Neto,Ricardo   Artigiani; Saad,Sarhan  Sidney; Forones,Nora   Manoukian

doi:10.3892/ol.2013.1606

December 2013 Volume 6 Issue 6

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

December 2013 Volume 6 Issue 6

Full Size Image

Article

DNA methylation as an epigenetic biomarker in colorectal cancer

Authors:
- Tiago Donizetti Silva
- Veronica Marques Vidigal
- Aledson Vitor Felipe
- Jacqueline Miranda De Lima
- Ricardo Artigiani Neto
- Sarhan Sidney Saad
- Nora Manoukian Forones
View Affiliations / Copyright

Affiliations: Oncology Group, Gastroenterology Division, Federal University of São Paulo, São Paulo 04023‑900, Brazil, Department of Pathology, Federal University of São Paulo, São Paulo 04023‑900, Brazil, Department of Surgery, Federal University of São Paulo, São Paulo 04023‑900, Brazil
Pages: 1687-1692
|
Published online on: October 7, 2013

https://doi.org/10.3892/ol.2013.1606
Expand metrics +

Abstract

Sporadic colorectal cancer (CRC) is a consequence of the accumulation of genetic and epigenetic alterations that result in the transformation of normal colonic epithelial cells to adenocarcinomas. Studies have indicated that a common event in the tumorigenesis of CRC is the association of global hypomethylation with discrete hypermethylation at the promoter regions of specific genes that are involved in cell cycle regulation, DNA repair, apoptosis, angiogenesis, adhesion and invasion. The present study aimed to investigate the epigenetic changes (DNA methylation) in 24 candidate genes in CRC. A total of 10 candidate hypermethylated (HM) and unmethylated (UM) genes were identified that may be useful epigenetic markers for non‑invasive CRC screening. The five genes that had the highest average UM percentages in the control group were MLH1 (71.7%), DKK2 (69.6%), CDKN2A (68.4%), APC (67.5%) and hsa‑mir‑342 (67.4%). RUNX3 (58.9%), PCDH10 (55.5%), SFRP5 (52.1%), IGF2 (50.4%) and Hnf1b (50.0%) were the five genes with the highest average HM percentages in the test group. In summary, the present preliminary study identified the methylation profiles of normal and cancerous colonic epithelial tissues, and provided the groundwork for future large‑scale methylation studies.

View Figures

View References

1	INCA. 2013, Instituto Nacional do Câncer. Ministério da Saúde. http://www.inca.gov.br/estimativa/2012/. Accessed January 10, 2013
2	Kim MS, Lee J and Sidransky D: DNA methylation markers in colorectal cancer. Cancer Metastasis Rev. 29:181–206. 2010. View Article : Google Scholar : PubMed/NCBI
3	Pellegrini ML, Argibay P and Gómez DE: Genetics and epigenetics of colorectal cancer. Acta Gastroenterol Latinoam. 41:247–261. 2011.(In Spanish).
4	Toribara NW and Sleisenger MH: Screening for colorectal cancer. N Eng J Med. 332:861–867. 1995. View Article : Google Scholar : PubMed/NCBI
5	Winawer SJ: Colorectal cancer screening. Best Pract Res Clin Gastroenterol. 21:1031–1048. 2007. View Article : Google Scholar
6	Pignone MP and Lewis CL: Using quality improvement techniques to increase colon cancer screening. Am J Med. 122:419–420. 2009. View Article : Google Scholar : PubMed/NCBI
7	Atkin W: Options for screening for colorectal cancer. Scand J Gastroenterol Suppl. 237:13–16. 2003. View Article : Google Scholar : PubMed/NCBI
8	Imperiale TF, Ransohoff DF, Itzkowitz SH, et al: Fecal DNA versus fecal occult blood for colorectal-cancer screening in an average-risk population. N Engl J Med. 351:2704–2714. 2004. View Article : Google Scholar : PubMed/NCBI
9	Grützmann R, Molnar B, Pilarsky C, et al: Sensitive detection of colorectal cancer in peripheral blood by septin 9 DNA methylation assay. PLoS One. 3:e37592008.PubMed/NCBI
10	Grady WM and Carethers JM: Genomic and epigenetic instability in colorectal cancer pathogenesis. Gastroenterology. 135:1079–1099. 2008. View Article : Google Scholar : PubMed/NCBI
11	Vogelstein B, Fearon ER, Hamilton SR, et al: Genetic alterations during colorectal-tumor development. N Eng J Med. 319:525–532. 1988. View Article : Google Scholar : PubMed/NCBI
12	Carmona FJ and Esteller M: Epigenomics of human colon cancer. Mutat Res. 693:53–60. 2010. View Article : Google Scholar : PubMed/NCBI
13	Rawson JB and Bapat B: Epigenetic biomarkers in colorectal cancer diagnostics. Expert Rev Mol Diagn. 12:499–509. 2012. View Article : Google Scholar : PubMed/NCBI
14	Conover WI: Practcal Nonparametric Statistics. 1st edition. John Wiley & Sons, Inc; New York, NY, USA: 1971
15	Daniel WW and Cross CL: Biostatistics: a foundation for analysis in the health sciences. 6th edition. John Wiley; Georgia, USA: 1995
16	Migheli F and Migliore L: Epigenetics of colorectal cancer. Clin Genet. 81:312–318. 2012. View Article : Google Scholar
17	Lange CP, Campan M, Hinoue T, et al: Genome-scale discovery of DNA-methylation biomarkers for blood-based detection of colorectal cancer. PLoS One. 7:e502662012. View Article : Google Scholar : PubMed/NCBI
18	Karpf AR and Jones DA: Reactivating the expression of methylation silenced genes in human cancer. Oncogene. 21:5496–5503. 2012. View Article : Google Scholar : PubMed/NCBI
19	Schuebel KE, Chen W, Cope L, et al: Comparing the DNA hypermethylome with gene mutations in human colorectal cancer. PLoS Genet. 3:1709–1723. 2007. View Article : Google Scholar : PubMed/NCBI
20	Lofton-Day C, Model F, Devos T, et al: DNA methylation biomarkers for blood-based colorectal cancer screening. Clin Chem. 54:414–423. 2008. View Article : Google Scholar : PubMed/NCBI
21	Goel A and Boland CR: Epigenetics of colorectal cancer. Gastroenterology. 143:1442–1460. 2012. View Article : Google Scholar
22	Ausch C, Kim YH, Tsuchiya KD, et al: Comparative analysis of PCR-based biomarker assay methods for colorectal polyp detection from fecal DNA. Clin Chem. 55:1559–63. 2009. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

DNA methylation as an epigenetic biomarker in colorectal cancer

This article is mentioned in:

Abstract

Figure 1

Figure 2

Related Articles