Abstract
DNA methylation is a key mechanism of colorectal carcinogenesis. Analysis of aberrantly methylation in stool DNA might provide a novel strategy for noninvasive detection of colorectal cancer (CRC). To explore the feasibility of this approach, we have assessed the methylation status of secreted frizzled-related protein gene 2 (SFRP2) in stool samples from patients with CRC with respect to a series of healthy individuals and patients with benign colorectal diseases, using methylation-specific polymerase chain reaction. Methylated SFRP2 occurs in 94.2%, 52.4%, 37.5%, and 16.7% of patients with CRC, adenomas, hyperplstic polyps, and ulcerative colitis, respectively. Of the 24 normal individuals, only 1 revealed methylated DNA. The pilot study revealed that aberrant methylated SFRP2 could be detected frequently in stools from patients with CRC and precancerous lesions. Methylation testing of fecal DNA may be a simple, promising, and noninvasive screening tool for colorectal neoplasia.
Similar content being viewed by others
References
Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, Thun MJ (2006) Cancer statistics. CA Cancer J Clin 56:106–130
Syngal S, Chung D, Willett C, Schoetz D, Schroy P, Stoffel E, Jagadeesh D, Morel K, Ross M (2002) Stool DNA analysis for the detection and follow-up of colorectal cancer (CRC) and advanced adenomas (AA): sensitivity in a prospective series. Am J Gastroenterol 197(Suppl):S109
Ahlquist DA, Skoletsky JE, Boynton KA, Harrington JJ, Mahoney DW, Pierceall WE, Thibodeau SN, Shuber AP (2000) Colorectal cancer screening by detection of altered human DNA in stool: feasibility of a multitarget assay panel. Astroenterology 119:1219–1227
Dong SM, Traverso G, Johnson C, Geng L, Favis R, Boynton K, Hibi K, Goodman SN, D’Allessio M, Paty P, Hamilton SR, Sidransky D, Barany F, Levin B, Shuber A, Kinzler KW, Vogelstein B, Jen J (2001) Detecting colorectal cancer in stool with the use of multiple genetic targets. J Natl Cancer Inst 93:858–865
Tagore KS, Lawson MJ, Yucaitis JA, Gage R, Orr T, Shuber AP, Ross ME (2003) Sensitivity and specificity of a stool DNA: multitarget assay panel for the detection of advanced colorectal neoplasia. Clin Colorectal Cancer 3:47–53
Jones PA, Baylin SB (2002) The fundamental role of epigenetic events in cancer. Nat Rev Genet 3:415–428
Baylin SB, Ohm JE (2006) Epigenetic gene silencing in cancer—a mechanism for early oncogenic pathway addiction? Nature 6:107–116
Kondo Y, Issa JP (2004) Epigenetic changes in colorectal cancer. Cancer Metastasis Rev 23:29–39
Chan AO, Broaddus RR, Houlihan PS, Issa JP, Hamilton SR, Rashid A (2002) CpG island methylation in aberrant crypt foci of the colorectum. Am J Pathol 160:1823–1830
Belshaw NJ, Elliott GO, Williams EA, Bradburn DM, Mills SJ, Mathers JC, Johnson IT (2004) Use of DNA from human stools to detect aberrant CpG island methylation of genes implicated in colorectal cancer. Cancer Epidemiol Biomarkers Prev 13:1495–150
Leung WK, To KF, Man EP, Chan MW, Bai AH, Hui AJ, Chan FK, Lee JF, Sung JJ (2004) Detection of epigenetic changes in fecal DNA as a molecular screening test for colorectal cancer: a feasibility study. Clin Chem 50:2179–2182
Müller HM, Oberwalder M, Fiegl H, Morandell M, Goebel G, Zitt M, Mühlthaler M, Öfner D, Margreiter R, Widschwendter M (2004) Methylation changes in faecal DNA: a marker for colorectal cancer screening? Lancet 363:1283–1285
Petko Z, Ghiassi M, Shuber A, Gorham J, Smalley W, Washington MK, Schultenover S, Gautam S, Markowitz SD, Grady WM (2005) Aberrantly methylated CDKN2A, MGMT, and MLH1 in colon polyps and in fecal DNA from patients with colorectal polyps. Clin Cancer Res 11:1203–1209
Lenhard K, Bommer GT, Asutay S, Schauer R, Brabletz T, Göke B, Lamerz R, Kolligs FT (2005) Analysis of promoter methylation in stool: a novel method for the detection of colorectal cancer. Clin Gastroenterol Hepatol 3:142–149
Herman JG, Graff JR, Myöhänen S, Nelkin BD, Baylin SB (1996) Methylation-specific PCR, a novel PCR assay for methylation Status of CpG islands. Proc Natl Acad Sci USA 93:9821–9826
Suzuki H, Gabrielson E, Chen W, Anbazhagan R, van Engeland M, Weijenberg MP, Herman JG, Baylin SB (2002) A genomic screen for genes upregulated by demethylation and histone deacetylase inhibition in human colorectal cancer. Nat Genet 31:141–149
Suzuki H, Watkins DN, Jair KW, Schuebel KE, Markowitz SD, Dong Chen W, Pretlow TP, Yang B, Akiyama Y, Van Engeland M, Toyota M, Tokino T, Hinoda Y, Imai K, Herman JG, Baylin SB (2004) Epigenetic inactivation of SFRP genes allows constitutive WNT signaling in colorectal cancer. Nat Genet 36:417–422
Kinzler KW, Vogelstein B (1996) Lessons from hereditary colorectal cancer. Cell 87:159–170
Wynter CV, Walsh MD, Higuchi T, Leggett BA, Young J, Jass JR (2004) Methylation patterns define two types of hyperplastic polyp associated with colorectal cancer. Gut 53:573–580
Pabby AJ, Suneja A, Heeren T, Farraye FA (2005) Flexible sigmoidoscopy for colorectal cancer screening in the elderly. Dig Dis Sci 50:2147–2152
Acknowledgment
This work was supported in part by a grant from the Scientific and Technologic Bureau of Wuxi (CS055010).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Huang, Z., Li, L. & Wang, J. Hypermethylation of SFRP2 as a Potential Marker for Stool-Based Detection of Colorectal Cancer and Precancerous Lesions. Dig Dis Sci 52, 2287–2291 (2007). https://doi.org/10.1007/s10620-007-9755-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10620-007-9755-y