JOURNAL BROWSE
Search
Advanced SearchSearch Tips
Sensitive and Noninvasive Detection of Aberrant SFRP2 and MGMT-B Methylation in Iranian Patients with Colon Polyps
facebook(new window)  Pirnt(new window) E-mail(new window) Excel Download
 Title & Authors
Sensitive and Noninvasive Detection of Aberrant SFRP2 and MGMT-B Methylation in Iranian Patients with Colon Polyps
Naini, M Alizade; Mokarram, P; Kavousipour, S; Zare, N; Atapour, A; Zarin, M Hassan; Mehrabani, G; Borji, M;
  PDF(new window)
 Abstract
Background: The pathogenesis of sporadic colorectal cancer (CRC) is influenced by the patient genetic background and environmental factors. Based on prior understanding, these are classified in two major pathways of genetic instability. Microsatellite instability (MSI) and CPG island methylator phenotype (CIMP) are categorized as features of the hypermethylated prototype, and chromosomal instability (CIN) is known to be indicative of the non-hypermethylated category. Secreted frizzled related protein 2 (SFRP2), APC1A in WNT signaling pathway and the DNA repair gene, O6-methylguanine-DNA methyltransferase (MGMT), are frequently hypermethylated in colorectal cancer. Detection of methylated DNA as a biomarker by easy and inexpensive methods might improve the quality of life of patients with CRC via early detection of cancer or a precancerous condition. Aim: To evaluate the rate of SFRP2 and MGMT hypermethylation in both polyp tissue and serum of patients in south Iran as compared with matched control normal population corresponding samples. Materials and Methods: Methylation-specific PCR was used to detect hypermethylation in DNA extracted from 48 polypoid tissue samples and 25 healthy individuals. Results: Of total polyp samples, 89.5% had at least one promoter gene hypermethylation. The most frequent methylated locus was SFRP2 followed by MGMT-B (81.2 and 66.6 percent respectively). Serologic detection of hypermethylation was 95% sensitive as compared with polyp tissue. No hypermethylation was detected in normal tissue and serum and its detection in patients with polyps, especially of serrated type, was specific. Conclusions: Serologic investigation for detection of MGMT-B, SFRP2 hypermethylation could facilitate prioritization of high risk patients for colonoscopic polyp detection and excision.
 Keywords
Colorectal cancer;polyp;MGMT;SFRP2;APC;methylation;serum diagnosis;
 Language
English
 Cited by
1.
Epigenetic biomarkers in colorectal cancer: premises and prospects, Biomarkers, 2016, 1366-5804, 1  crossref(new windwow)
 References
1.
Bishehsari F, Mahdavinia M, Vacca M, et al (2014). Epidemiological transition of colorectal cancer in developing countries: Environmental factors, molecular pathways, and opportunities for prevention. World J Gastroenterol, 20, 6055-72. crossref(new window)

2.
Carethers JM, Jung BH (2015). Genetics and Genetic Biomarkers in Sporadic Colorectal Cancer. Gastroenterol, 149, 1177- 90.e3. crossref(new window)

3.
Chang E, Park DI, Kim YJ, et al (2010). Detection of colorectal neoplasm using promoter methylation of ITGA4, SFRP2, and p16 in stool samples: a preliminary report in Korean patients. Hepatogastroenterol, 57, 720-7.

4.
Coppede F, Lopomo A, Spisni R, et al (2014). Genetic and epigenetic biomarkers for diagnosis, prognosis and treatment of colorectal cancer. World J Gastroenterol, 20, 943-56. crossref(new window)

5.
De Maio G, Rengucci C, Zoli W, et al (2014). Circulating and stool nucleic acid analysis for colorectal cancer diagnosis. World J Gastroenterol, 20, 957-67. crossref(new window)

6.
Esteller M, Hamilton SR, Burger PC, et al (1999). Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is a common event in primary human neoplasia. Cancer Res, 59, 793-7.

7.
Feldman M, Friedman LS (2010). Sleisenger and Fordtran's Gastrointestinal and Liver Disease. In Eds Saunders elsevier. Philadelphia.

8.
Fisher JA, Fikry C, Troxel AB (2006). Cutting cost and increasing access to colorectal cancer screening: another approach to following the guidelines. Cancer Epidemiol Biomarkers Prev, 15, 108-13. crossref(new window)

9.
Hagrass HA, Pasha HF, Shaheen MA, et al (2014). Methylation status and protein expression of RASSF1A in breast cancer patients. Mol Biol Rep, 41, 57-65. crossref(new window)

10.
Halford S, Rowan A, Sawyer E, et al (2005). O(6)-methylguanine methyltransferase in colorectal cancers: detection of mutations, loss of expression, and weak association with G:C>A:T transitions. Gut, 54, 797-802. crossref(new window)

11.
Hassanzade J, Molavi EVH, Farahmand M, et al (2011). Incidence and mortality rate of common gastrointestinal cancers in south of Iran, a population based study. Iran J Cancer Prev, 4, 163-9.

12.
Heitzer E, Ulz P, Geigl JB (2015). Circulating tumor DNA as a liquid biopsy for cancer. Clin Chem, 61, 112-23. crossref(new window)

13.
Herbst A, Rahmig K, Stieber P, et al (2011). Methylation of NEUROG1 in serum is a sensitive marker for the detection of early colorectal cancer. Am J Gastroenterol, 106, 1110-8. crossref(new window)

14.
Herman JG, Baylin SB (2003). Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med, 349, 2042-54. crossref(new window)

15.
Hibi K, Goto T, Mizukami H, et al (2009). MGMT gene is aberrantly methylated from the early stages of colorectal cancers. Hepatogastroenterol, 56, 1642-4.

16.
Huang ZH, Li LH, Yang F, et al (2007). Detection of aberrant methylation in fecal DNA as a molecular screening tool for colorectal cancer and precancerous lesions. World J Gastroenterol, 13, 950-4. crossref(new window)

17.
Kim MS, Lee J, Sidransky D (2010). DNA methylation markers in colorectal cancer. Cancer Metastasis Rev, 29, 181-206. crossref(new window)

18.
Kycler W, Szarzynska B, Lozinski C, et al (2012). Analysis of O6-methylguanine-DNA methyltransferase methylation status in sporadic colon polyps. Rep Pract Oncol Radiother, 17, 13-8. crossref(new window)

19.
Lee BB, Lee EJ, Jung EH, et al (2009). Aberrant methylation of APC, MGMT, RASSF2A, and Wif-1 genes in plasma as a biomarker for early detection of colorectal cancer. Clin Cancer Res, 15, 6185-91. crossref(new window)

20.
Leggett BA, Hewett DG (2015). Colorectal cancer screening. Intern Med J, 45, 6-15.

21.
Levin B, Lieberman DA, McFarland B, et al (2008). Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. CA Cancer J Clin, 58, 130-60. crossref(new window)

22.
Lo Nigro C, Wang H, McHugh A, et al (2013). Methylated tissue factor pathway inhibitor 2 (TFPI2) DNA in serum is a biomarker of metastatic melanoma. J Invest Dermatol, 133, 1278-85. crossref(new window)

23.
Lofton-Day C, Model F, Devos T, et al (2008). DNA methylation biomarkers for blood-based colorectal cancer screening. Clin Chem, 54, 414-23. crossref(new window)

24.
Lu H, Huang S, Zhang X, et al (2014). DNA methylation analysis of SFRP2, GATA4/5, NDRG4 and VIM for the detection of colorectal cancer in fecal DNA. Oncol Lett, 8, 1751-6. crossref(new window)

25.
Mokarram P, Kavousipour S, Sarabi MM, et al (2015). MGMT-B gene promoter hypermethylation in patients with inflammatory bowel disease - a novel finding. Asian Pac J Cancer Prev, 16, 1945-52. crossref(new window)

26.
Mokarram P, Naghibalhossaini F, Saberi Firoozi M, et al (2008). Methylenetetrahydrofolate reductase C677T genotype affects promoter methylation of tumor-specific genes in sporadic colorectal cancer through an interaction with folate/ vitamin B12 status. World J Gastroenterol, 14, 3662-71. crossref(new window)

27.
Mokarram P, Zamani M, Kavousipour S, et al (2013). Different patterns of DNA methylation of the two distinct O6- methylguanine-DNA methyltransferase (O6-MGMT) promoter regions in colorectal cancer. Mol Biol Rep, 40, 3851-7. crossref(new window)

28.
Muller HM, Oberwalder M, Fiegl H, et al (2004). Methylation changes in faecal DNA: a marker for colorectal cancer screening? Lancet, 363, 1283-5. crossref(new window)

29.
Murakami T, Mitomi H, Saito T, et al (2015). Distinct WNT/ beta-catenin signaling activation in the serrated neoplasia pathway and the adenoma-carcinoma sequence of the colorectum. Mod Pathol, 28, 146-58. crossref(new window)

30.
Naghibalhossaini F, Zamani M, Mokarram P, et al (2012). Epigenetic and genetic analysis of WNT signaling pathway in sporadic colorectal cancer patients from Iran. Mol Biol Rep, 39, 6171-8. crossref(new window)

31.
Oberwalder M, Zitt M, Wontner C, et al (2008). SFRP2 methylation in fecal DNA--a marker for colorectal polyps. Int J Colorectal Dis, 23, 15-9.

32.
Oh T, Kim N, Moon Y, et al (2013). Genome-wide identification and validation of a novel methylation biomarker, SDC2, for blood-based detection of colorectal cancer. J Mol Diagn, 15, 498-507. crossref(new window)

33.
Okugawa Y, Grady WM, Goel A (2015). Epigenetic Alterations in Colorectal Cancer: Emerging Biomarkers. Gastroenterol, 149, 1204-25. crossref(new window)

34.
Psofaki V, Kalogera C, Tzambouras N, et al (2010). Promoter methylation status of hMLH1, MGMT, and CDKN2A/p16 in colorectal adenomas. World J Gastroenterol, 16, 3553-60. crossref(new window)

35.
Salehi R, Mohammadi M, Emami MH, et al (2012). Methylation pattern of SFRP1 promoter in stool sample is a potential marker for early detection of colorectal cancer. Adv Biomed Res, 1, 87. crossref(new window)

36.
Segditsas S, Sieber OM, Rowan A, et al (2008). Promoter hypermethylation leads to decreased APC mRNA expression in familial polyposis and sporadic colorectal tumours, but does not substitute for truncating mutations. Exp Mol Pathol, 85, 201-6. crossref(new window)

37.
Segditsas S, Tomlinson I (2006). Colorectal cancer and genetic alterations in the Wnt pathway. Oncogene, 25, 7531-7. crossref(new window)

38.
Shah R, Jones E, Vidart V, et al (2014). Biomarkers for early detection of colorectal cancer and polyps: systematic review. Cancer Epidemiol Biomarkers Prev, 23, 1712-28. crossref(new window)

39.
Shen L, Kondo Y, Rosner GL, et al (2005). MGMT promoter methylation and field defect in sporadic colorectal cancer. J Natl Cancer Inst, 97, 1330-8. crossref(new window)

40.
Silva AL, Dawson SN, Arends MJ, et al (2014). Boosting Wnt activity during colorectal cancer progression through selective hypermethylation of Wnt signaling antagonists. BMC Cancer, 14, 891. crossref(new window)

41.
Stoffel EM, Boland CR (2015). Genetics and Genetic Testing in Hereditary Colorectal Cancer. Gastroenterol, 149, 1191-203. crossref(new window)

42.
Stracci F, Zorzi M, Grazzini G (2014). Colorectal Cancer Screening: Tests, Strategies, and Perspectives. Frontiers Public Health, 2, 210.

43.
Summers T, Langan RC, Nissan A, et al (2013). Serum-based DNA methylation biomarkers in colorectal cancer: potential for screening and early detection. J Cancer, 4, 210-6. crossref(new window)

44.
Takane K, Midorikawa Y, Yagi K, et al (2014). Aberrant promoter methylation of PPP1R3C and EFHD1 in plasma of colorectal cancer patients. Cancer Med, 3, 1235-45. crossref(new window)

45.
Takeda M, Nagasaka T, Dong-Sheng S, et al (2011). Expansion of CpG methylation in the SFRP2 promoter region during colorectal tumorigenesis. Acta Med Okayama, 65, 169-77.

46.
Tang D, Liu J, Wang DR, et al (2011). Diagnostic and prognostic value of the methylation status of secreted frizzled-related protein 2 in colorectal cancer. Clin Invest Med, 34, 88-95. crossref(new window)

47.
Tanzer M, Balluff B, Distler J, et al (2010). Performance of epigenetic markers SEPT9 and ALX4 in plasma for detection of colorectal precancerous lesions. PLoS One, 5, 9061. crossref(new window)

48.
van Bemmel D, Lenz P, Liao LM, et al (2012). Correlation of LINE-1 methylation levels in patient-matched buffy coat, serum, buccal cell, and bladder tumor tissue DNA samples. Cancer Epidemiol Biomarkers Prev, 21, 1143-8. crossref(new window)

49.
Voorham QJ, Janssen J, Tijssen M, et al (2013). Promoter methylation of Wnt-antagonists in polypoid and nonpolypoid colorectal adenomas. BMC Cancer, 13, 603. crossref(new window)

50.
Wang D-R, Tang D (2008). Hypermethylated SFRP2 gene in fecal DNA is a high potential biomarker for colorectal cancer noninvasive screening. World J Gastroenterol, 14, 524-31. crossref(new window)

51.
Wang X, Kuang YY, Hu XT (2014). Advances in epigenetic biomarker research in colorectal cancer. World J Gastroenterol, 20, 4276-87. crossref(new window)

52.
Wang Z, Jiang W, Wang Y, et al (2015). promoter methylation in serum and cerebrospinal fluid as a tumor-specific biomarker of glioma. Biomed Rep, 3, 543-8. crossref(new window)

53.
Whitehall VL, Walsh MD, Young J, et al (2001). Methylation of O-6-methylguanine DNA methyltransferase characterizes a subset of colorectal cancer with low-level DNA microsatellite instability. Cancer Res, 61, 827-30.

54.
Yi JM, Dhir M, Guzzetta AA, et al (2012). DNA methylation biomarker candidates for early detection of colon cancer. Tumour Biol, 33, 363-72. crossref(new window)

55.
Ying Y, Tao Q (2009). Epigenetic disruption of the WNT/betacatenin signaling pathway in human cancers. Epigenetics, 4, 307-12. crossref(new window)

56.
Zhang W, Bauer M, Croner RS, et al (2007). DNA stool test for colorectal cancer: hypermethylation of the secreted frizzledrelated protein-1 gene. Dis Colon Rectum, 50, 1618-26. crossref(new window)

57.
Zhang X, Song YF, Lu HN, et al (2015). Combined detection of plasma GATA5 and SFRP2 methylation is a valid noninvasive biomarker for colorectal cancer and adenomas. World J Gastroenterol, 21, 2629-37. crossref(new window)

58.
Zou H, Harrington JJ, Shire AM, et al (2007). Highly methylated genes in colorectal neoplasia: implications for screening. Cancer Epidemiol Biomarkers Prev, 16, 2686-96. crossref(new window)