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Published in: Molecular Cancer 1/2011

Open Access 01-12-2011 | Research

Identification of an epigenetic biomarker panel with high sensitivity and specificity for colorectal cancer and adenomas

Authors: Guro E Lind, Stine A Danielsen, Terje Ahlquist, Marianne A Merok, Kim Andresen, Rolf I Skotheim, Merete Hektoen, Torleiv O Rognum, Gunn I Meling, Geir Hoff, Michael Bretthauer, Espen Thiis-Evensen, Arild Nesbakken, Ragnhild A Lothe

Published in: Molecular Cancer | Issue 1/2011

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Abstract

Background

The presence of cancer-specific DNA methylation patterns in epithelial colorectal cells in human feces provides the prospect of a simple, non-invasive screening test for colorectal cancer and its precursor, the adenoma. This study investigates a panel of epigenetic markers for the detection of colorectal cancer and adenomas.

Methods

Candidate biomarkers were subjected to quantitative methylation analysis in test sets of tissue samples from colorectal cancers, adenomas, and normal colonic mucosa. All findings were verified in independent clinical validation series. A total of 523 human samples were included in the study. Receiver operating characteristic (ROC) curve analysis was used to evaluate the performance of the biomarker panel.

Results

Promoter hypermethylation of the genes CNRIP1, FBN1, INA, MAL, SNCA, and SPG20 was frequent in both colorectal cancers (65-94%) and adenomas (35-91%), whereas normal mucosa samples were rarely (0-5%) methylated. The combined sensitivity of at least two positives among the six markers was 94% for colorectal cancers and 93% for adenoma samples, with a specificity of 98%. The resulting areas under the ROC curve were 0.984 for cancers and 0.968 for adenomas versus normal mucosa.

Conclusions

The novel epigenetic marker panel shows very high sensitivity and specificity for both colorectal cancers and adenomas. Our findings suggest this biomarker panel to be highly suitable for early tumor detection.
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Literature
1.
go back to reference Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ: Cancer statistics, 2008. CA Cancer J Clin. 2008, 58: 71-96. 10.3322/CA.2007.0010CrossRefPubMed Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ: Cancer statistics, 2008. CA Cancer J Clin. 2008, 58: 71-96. 10.3322/CA.2007.0010CrossRefPubMed
2.
go back to reference Levin B, Lieberman DA, McFarland B, Andrews KS, Brooks D, Bond J, Dash C, Giardiello FM, Glick S, Johnson CD, Levin TR, Pickhardt PJ, Rex DK, Smith RA, Thorson A, Winawer SJ: 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. Gastroenterology. 2008, 134: 1570-1595. 10.1053/j.gastro.2008.02.002CrossRefPubMed Levin B, Lieberman DA, McFarland B, Andrews KS, Brooks D, Bond J, Dash C, Giardiello FM, Glick S, Johnson CD, Levin TR, Pickhardt PJ, Rex DK, Smith RA, Thorson A, Winawer SJ: 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. Gastroenterology. 2008, 134: 1570-1595. 10.1053/j.gastro.2008.02.002CrossRefPubMed
3.
go back to reference Bretthauer M: Evidence for colorectal cancer screening. Best Pract Res Clin Gastroenterol. 2010, 24: 417-425. 10.1016/j.bpg.2010.06.005CrossRefPubMed Bretthauer M: Evidence for colorectal cancer screening. Best Pract Res Clin Gastroenterol. 2010, 24: 417-425. 10.1016/j.bpg.2010.06.005CrossRefPubMed
4.
go back to reference Atkin WS, Edwards R, Kralj-Hans I, Wooldrage K, Hart AR, Northover JM, Parkin DM, Wardle J, Duffy SW, Cuzick J: Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer: a multicentre randomised controlled trial. Lancet. 2010, 375: 1624-1633. 10.1016/S0140-6736(10)60551-XCrossRefPubMed Atkin WS, Edwards R, Kralj-Hans I, Wooldrage K, Hart AR, Northover JM, Parkin DM, Wardle J, Duffy SW, Cuzick J: Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer: a multicentre randomised controlled trial. Lancet. 2010, 375: 1624-1633. 10.1016/S0140-6736(10)60551-XCrossRefPubMed
5.
go back to reference van DL, Kuipers EJ, van Leerdam ME: Performance improvements of stool-based screening tests. Best Pract Res Clin Gastroenterol. 2010, 24: 479-492. 10.1016/j.bpg.2010.03.009 van DL, Kuipers EJ, van Leerdam ME: Performance improvements of stool-based screening tests. Best Pract Res Clin Gastroenterol. 2010, 24: 479-492. 10.1016/j.bpg.2010.03.009
6.
go back to reference Rashid A, Shen L, Morris JS, Issa JP, Hamilton SR: CpG island methylation in colorectal adenomas. Am J Pathol. 2001, 159: 1129-1135. 10.1016/S0002-9440(10)61789-0PubMedCentralCrossRefPubMed Rashid A, Shen L, Morris JS, Issa JP, Hamilton SR: CpG island methylation in colorectal adenomas. Am J Pathol. 2001, 159: 1129-1135. 10.1016/S0002-9440(10)61789-0PubMedCentralCrossRefPubMed
7.
go back to reference Chan AO, Broaddus RR, Houlihan PS, Issa JP, Hamilton SR, Rashid A: CpG island methylation in aberrant crypt foci of the colorectum. Am J Pathol. 2002, 160: 1823-1830. 10.1016/S0002-9440(10)61128-5PubMedCentralCrossRefPubMed Chan AO, Broaddus RR, Houlihan PS, Issa JP, Hamilton SR, Rashid A: CpG island methylation in aberrant crypt foci of the colorectum. Am J Pathol. 2002, 160: 1823-1830. 10.1016/S0002-9440(10)61128-5PubMedCentralCrossRefPubMed
8.
go back to reference Chang E, Park DI, Kim YJ, Kim BK, Park JH, Kim HJ, Cho YK, Sohn CI, Jeon WK, Kim BI, Kim HD, Kim DH, Kim YH: Detection of colorectal neoplasm using promoter methylation of ITGA4, SFRP2, and p16 in stool samples: a preliminary report in Korean patients. Hepatogastroenterology. 2010, 57: 720-727.PubMed Chang E, Park DI, Kim YJ, Kim BK, Park JH, Kim HJ, Cho YK, Sohn CI, Jeon WK, Kim BI, Kim HD, Kim DH, Kim YH: Detection of colorectal neoplasm using promoter methylation of ITGA4, SFRP2, and p16 in stool samples: a preliminary report in Korean patients. Hepatogastroenterology. 2010, 57: 720-727.PubMed
9.
go back to reference Lind GE, Raiborg C, Danielsen SA, Rognum TO, Thiis-Evensen E, Hoff G, Nesbakken A, Stenmark H, Lothe RA: SPG20, a novel biomarker in colorectal carcinogenesis, encodes a regulator of cytokinesis. Oncogene. 2011, 1-12. Lind GE, Raiborg C, Danielsen SA, Rognum TO, Thiis-Evensen E, Hoff G, Nesbakken A, Stenmark H, Lothe RA: SPG20, a novel biomarker in colorectal carcinogenesis, encodes a regulator of cytokinesis. Oncogene. 2011, 1-12.
10.
go back to reference Øster B, Thorsen K, Lamy P, Wojdacz TK, Hansen LL, Birkenkamp-Demtrõder K, Sørensen KD, Laurberg S, Ørntoft TF, Andersen CL: Identification and validation of highly frequent CpG island hypermethylation in colorectal adenomas and carcinomas. Int J Cancer. 2011, 10- Øster B, Thorsen K, Lamy P, Wojdacz TK, Hansen LL, Birkenkamp-Demtrõder K, Sørensen KD, Laurberg S, Ørntoft TF, Andersen CL: Identification and validation of highly frequent CpG island hypermethylation in colorectal adenomas and carcinomas. Int J Cancer. 2011, 10-
11.
go back to reference Müller HM, Oberwalder M, Fiegl H, Morandell M, Goebel G, Zitt M, Mühlthaler M, Öfner D, Margreiter R, Widschwendter M: Methylation changes in faecal DNA: a marker for colorectal cancer screening?. Lancet. 2004, 363: 1283-1285. 10.1016/S0140-6736(04)16002-9CrossRefPubMed Müller HM, Oberwalder M, Fiegl H, Morandell M, Goebel G, Zitt M, Mühlthaler M, Öfner D, Margreiter R, Widschwendter M: Methylation changes in faecal DNA: a marker for colorectal cancer screening?. Lancet. 2004, 363: 1283-1285. 10.1016/S0140-6736(04)16002-9CrossRefPubMed
12.
go back to reference Chen WD, Han ZJ, Skoletsky J, Olson J, Sah J, Myeroff L, Platzer P, Lu S, Dawson D, Willis J, Pretlow TP, Lutterbaugh J, Kasheri L, Willson JK, Rao JS, Shuber A, Markowitz SD: Detection in fecal DNA of colon cancer-specific methylation of the nonexpressed vimentin gene. J Natl Cancer Inst. 2005, 97: 1124-1132. 10.1093/jnci/dji204CrossRefPubMed Chen WD, Han ZJ, Skoletsky J, Olson J, Sah J, Myeroff L, Platzer P, Lu S, Dawson D, Willis J, Pretlow TP, Lutterbaugh J, Kasheri L, Willson JK, Rao JS, Shuber A, Markowitz SD: Detection in fecal DNA of colon cancer-specific methylation of the nonexpressed vimentin gene. J Natl Cancer Inst. 2005, 97: 1124-1132. 10.1093/jnci/dji204CrossRefPubMed
13.
go back to reference Zhang W, Bauer M, Croner RS, Pelz JO, Lodygin D, Hermeking H, Sturzl M, Hohenberger W, Matzel KE: DNA Stool Test for Colorectal Cancer: Hypermethylation of the Secreted Frizzled-Related Protein-1 Gene. Dis Colon Rectum. 2007, 50: 1618-1626. 10.1007/s10350-007-0286-6CrossRefPubMed Zhang W, Bauer M, Croner RS, Pelz JO, Lodygin D, Hermeking H, Sturzl M, Hohenberger W, Matzel KE: DNA Stool Test for Colorectal Cancer: Hypermethylation of the Secreted Frizzled-Related Protein-1 Gene. Dis Colon Rectum. 2007, 50: 1618-1626. 10.1007/s10350-007-0286-6CrossRefPubMed
14.
go back to reference Kim MS, Louwagie J, Carvalho B, Terhaar Sive Droste JS, Park HL, Chae YK, Yamashita K, Liu J, Ostrow KL, Ling S, Guerrero-Preston R, Demokan S, Yalniz Z, Dalay N, Meijer GA, van Criekinge W, Sidransky D: Promoter DNA methylation of oncostatin m receptor-beta as a novel diagnostic and therapeutic marker in colon cancer. PLoS ONE. 2009, 4: e6555- 10.1371/journal.pone.0006555PubMedCentralCrossRefPubMed Kim MS, Louwagie J, Carvalho B, Terhaar Sive Droste JS, Park HL, Chae YK, Yamashita K, Liu J, Ostrow KL, Ling S, Guerrero-Preston R, Demokan S, Yalniz Z, Dalay N, Meijer GA, van Criekinge W, Sidransky D: Promoter DNA methylation of oncostatin m receptor-beta as a novel diagnostic and therapeutic marker in colon cancer. PLoS ONE. 2009, 4: e6555- 10.1371/journal.pone.0006555PubMedCentralCrossRefPubMed
15.
go back to reference Kim MS, Lee J, Sidransky D: DNA methylation markers in colorectal cancer. Cancer Metastasis Rev. 2010, 29: 181-206. 10.1007/s10555-010-9207-6CrossRefPubMed Kim MS, Lee J, Sidransky D: DNA methylation markers in colorectal cancer. Cancer Metastasis Rev. 2010, 29: 181-206. 10.1007/s10555-010-9207-6CrossRefPubMed
16.
go back to reference Tang D, Liu J, Wang DR, Yu HF, Li YK, Zhang JQ: Diagnostic and prognostic value of the methylation status of secreted frizzled-related protein 2 in colorectal cancer. Clin Invest Med. 2011, 34: E88-E95.PubMed Tang D, Liu J, Wang DR, Yu HF, Li YK, Zhang JQ: Diagnostic and prognostic value of the methylation status of secreted frizzled-related protein 2 in colorectal cancer. Clin Invest Med. 2011, 34: E88-E95.PubMed
17.
go back to reference Herbst A, Rahmig K, Stieber P, Philipp A, Jung A, Ofner A, Crispin A, Neumann J, Lamerz R, Kolligs FT: Methylation of NEUROG1 in Serum Is a Sensitive Marker for the Detection of Early Colorectal Cancer. Am J Gastroenterol. 2011, 106: 1110-1118. 10.1038/ajg.2011.6CrossRefPubMed Herbst A, Rahmig K, Stieber P, Philipp A, Jung A, Ofner A, Crispin A, Neumann J, Lamerz R, Kolligs FT: Methylation of NEUROG1 in Serum Is a Sensitive Marker for the Detection of Early Colorectal Cancer. Am J Gastroenterol. 2011, 106: 1110-1118. 10.1038/ajg.2011.6CrossRefPubMed
18.
go back to reference Tänzer M, Balluff B, Distler J, Hale K, Leodolter A, Rocken C, Molnar B, Schmid R, Lofton-Day C, Schuster T, Ebert MP: Performance of epigenetic markers SEPT9 and ALX4 in plasma for detection of colorectal precancerous lesions. PLoS ONE. 2010, 5: e9061- 10.1371/journal.pone.0009061PubMedCentralCrossRefPubMed Tänzer M, Balluff B, Distler J, Hale K, Leodolter A, Rocken C, Molnar B, Schmid R, Lofton-Day C, Schuster T, Ebert MP: Performance of epigenetic markers SEPT9 and ALX4 in plasma for detection of colorectal precancerous lesions. PLoS ONE. 2010, 5: e9061- 10.1371/journal.pone.0009061PubMedCentralCrossRefPubMed
19.
go back to reference He Q, Chen HY, Bai EQ, Luo YX, Fu RJ, He YS, Jiang J, Wang HQ: Development of a multiplex MethyLight assay for the detection of multigene methylation in human colorectal cancer. Cancer Genet Cytogenet. 2010, 202: 1-10. 10.1016/j.cancergencyto.2010.05.018CrossRefPubMed He Q, Chen HY, Bai EQ, Luo YX, Fu RJ, He YS, Jiang J, Wang HQ: Development of a multiplex MethyLight assay for the detection of multigene methylation in human colorectal cancer. Cancer Genet Cytogenet. 2010, 202: 1-10. 10.1016/j.cancergencyto.2010.05.018CrossRefPubMed
20.
go back to reference Lind GE, Kleivi K, Meling GI, Teixeira MR, Thiis-Evensen E, Rognum TO, Lothe RA: ADAMTS1, CRABP1, and NR3C1 identified as epigenetically deregulated genes in colorectal tumorigenesis. Cell Oncol. 2006, 28: 259-272.PubMed Lind GE, Kleivi K, Meling GI, Teixeira MR, Thiis-Evensen E, Rognum TO, Lothe RA: ADAMTS1, CRABP1, and NR3C1 identified as epigenetically deregulated genes in colorectal tumorigenesis. Cell Oncol. 2006, 28: 259-272.PubMed
21.
go back to reference Lind GE, Ahlquist T, Lothe RA: DNA hypermethylation of MAL: a promising diagnostic biomarker for colorectal tumors. Gastroenterology. 2007, 132: 1631-1632. 10.1053/j.gastro.2007.03.003CrossRefPubMed Lind GE, Ahlquist T, Lothe RA: DNA hypermethylation of MAL: a promising diagnostic biomarker for colorectal tumors. Gastroenterology. 2007, 132: 1631-1632. 10.1053/j.gastro.2007.03.003CrossRefPubMed
22.
go back to reference Lind GE, Ahlquist T, Kolberg M, Berg M, Eknaes M, Alonso MA, Kallioniemi A, Meling GI, Skotheim RI, Rognum TO, Thiis-Evensen E, Lothe RA: Hypermethylated MAL gene - a silent marker of early colon tumorigenesis. J Transl Med. 2008, 6 (13): 13-PubMedCentralCrossRefPubMed Lind GE, Ahlquist T, Kolberg M, Berg M, Eknaes M, Alonso MA, Kallioniemi A, Meling GI, Skotheim RI, Rognum TO, Thiis-Evensen E, Lothe RA: Hypermethylated MAL gene - a silent marker of early colon tumorigenesis. J Transl Med. 2008, 6 (13): 13-PubMedCentralCrossRefPubMed
23.
go back to reference Kleivi K, Teixeira MR, Eknaes M, Diep CB, Jakobsen KS, Hamelin R, Lothe RA: Genome signatures of colon carcinoma cell lines. Cancer Genet Cytogenet. 2004, 155: 119-131. 10.1016/j.cancergencyto.2004.03.014CrossRefPubMed Kleivi K, Teixeira MR, Eknaes M, Diep CB, Jakobsen KS, Hamelin R, Lothe RA: Genome signatures of colon carcinoma cell lines. Cancer Genet Cytogenet. 2004, 155: 119-131. 10.1016/j.cancergencyto.2004.03.014CrossRefPubMed
24.
go back to reference Kunkel LM, Smith KD, Boyer SH, Borgaonkar DS, Wachtel SS, Miller OJ, Breg WR, Jones HW, Rary JM: Analysis of human Y-chromosome-specific reiterated DNA in chromosome variants. Proc Natl Acad Sci USA. 1977, 74: 1245-1249. 10.1073/pnas.74.3.1245PubMedCentralCrossRefPubMed Kunkel LM, Smith KD, Boyer SH, Borgaonkar DS, Wachtel SS, Miller OJ, Breg WR, Jones HW, Rary JM: Analysis of human Y-chromosome-specific reiterated DNA in chromosome variants. Proc Natl Acad Sci USA. 1977, 74: 1245-1249. 10.1073/pnas.74.3.1245PubMedCentralCrossRefPubMed
25.
go back to reference Meling GI, Lothe RA, Børresen AL, Hauge S, Graue C, Clausen OP, Rognum TO: Genetic alterations within the retinoblastoma locus in colorectal carcinomas. Relation to DNA ploidy pattern studied by flow cytometric analysis. Br J Cancer. 1991, 64: 475-480. 10.1038/bjc.1991.334PubMedCentralCrossRefPubMed Meling GI, Lothe RA, Børresen AL, Hauge S, Graue C, Clausen OP, Rognum TO: Genetic alterations within the retinoblastoma locus in colorectal carcinomas. Relation to DNA ploidy pattern studied by flow cytometric analysis. Br J Cancer. 1991, 64: 475-480. 10.1038/bjc.1991.334PubMedCentralCrossRefPubMed
26.
go back to reference Lothe RA, Peltomäki P, Meling GI, Aaltonen LA, Nyström-Lahti M, Pylkkänen L, Heimdal K, Andersen TI, Møller P, Rognum TO, Fosså SD, Haldorsen T, Langmark F, Brøgger A, de la CHapelle A, Børresen AL: Genomic instability in colorectal cancer: relationship to clinicopathological variables and family history. Cancer Res. 1993, 53: 5849-5852.PubMed Lothe RA, Peltomäki P, Meling GI, Aaltonen LA, Nyström-Lahti M, Pylkkänen L, Heimdal K, Andersen TI, Møller P, Rognum TO, Fosså SD, Haldorsen T, Langmark F, Brøgger A, de la CHapelle A, Børresen AL: Genomic instability in colorectal cancer: relationship to clinicopathological variables and family history. Cancer Res. 1993, 53: 5849-5852.PubMed
27.
go back to reference Thorstensen L, Lind GE, Løvig T, Diep CB, Meling GI, Rognum TO, Lothe RA: Genetic and Epigenetic Changes of Components Affecting the WNT Pathway in Colorectal Carcinomas Stratified by Microsatellite Instability. Neoplasia. 2005, 7: 99-108. 10.1593/neo.04448PubMedCentralCrossRefPubMed Thorstensen L, Lind GE, Løvig T, Diep CB, Meling GI, Rognum TO, Lothe RA: Genetic and Epigenetic Changes of Components Affecting the WNT Pathway in Colorectal Carcinomas Stratified by Microsatellite Instability. Neoplasia. 2005, 7: 99-108. 10.1593/neo.04448PubMedCentralCrossRefPubMed
28.
go back to reference Thiis-Evensen E, Hoff GS, Sauar J, Langmark F, Majak BM, Vatn MH: Population-based surveillance by colonoscopy: effect on the incidence of colorectal cancer. Telemark Polyp Study I. Scand J Gastroenterol. 1999, 34: 414-420. 10.1080/003655299750026443CrossRefPubMed Thiis-Evensen E, Hoff GS, Sauar J, Langmark F, Majak BM, Vatn MH: Population-based surveillance by colonoscopy: effect on the incidence of colorectal cancer. Telemark Polyp Study I. Scand J Gastroenterol. 1999, 34: 414-420. 10.1080/003655299750026443CrossRefPubMed
29.
go back to reference Bretthauer M, Gondal G, Larsen K, Carlsen E, Eide TJ, Grotmol T, Skovlund E, Tveit KM, Vatn MH, Hoff G: Design, organization and management of a controlled population screening study for detection of colorectal neoplasia: attendance rates in the NORCCAP study (Norwegian Colorectal Cancer Prevention). Scand J Gastroenterol. 2002, 37: 568-573. 10.1080/00365520252903125CrossRefPubMed Bretthauer M, Gondal G, Larsen K, Carlsen E, Eide TJ, Grotmol T, Skovlund E, Tveit KM, Vatn MH, Hoff G: Design, organization and management of a controlled population screening study for detection of colorectal neoplasia: attendance rates in the NORCCAP study (Norwegian Colorectal Cancer Prevention). Scand J Gastroenterol. 2002, 37: 568-573. 10.1080/00365520252903125CrossRefPubMed
30.
31.
go back to reference Weisenberger DJ, Campan M, Long TI, Kim M, Woods C, Fiala E, Ehrlich M, Laird PW: Analysis of repetitive element DNA methylation by MethyLight. Nucleic Acids Res. 2005, 33: 6823-6836. 10.1093/nar/gki987PubMedCentralCrossRefPubMed Weisenberger DJ, Campan M, Long TI, Kim M, Woods C, Fiala E, Ehrlich M, Laird PW: Analysis of repetitive element DNA methylation by MethyLight. Nucleic Acids Res. 2005, 33: 6823-6836. 10.1093/nar/gki987PubMedCentralCrossRefPubMed
32.
go back to reference Widschwendter M, Siegmund KD, Muller HM, Fiegl H, Marth C, Muller-Holzner E, Jones PA, Laird PW: Association of breast cancer DNA methylation profiles with hormone receptor status and response to tamoxifen. Cancer Res. 2004, 64: 3807-3813. 10.1158/0008-5472.CAN-03-3852CrossRefPubMed Widschwendter M, Siegmund KD, Muller HM, Fiegl H, Marth C, Muller-Holzner E, Jones PA, Laird PW: Association of breast cancer DNA methylation profiles with hormone receptor status and response to tamoxifen. Cancer Res. 2004, 64: 3807-3813. 10.1158/0008-5472.CAN-03-3852CrossRefPubMed
33.
go back to reference Melki JR, Vincent PC, Clark SJ: Concurrent DNA hypermethylation of multiple genes in acute myeloid leukemia. Cancer Res. 1999, 59: 3730-3740.PubMed Melki JR, Vincent PC, Clark SJ: Concurrent DNA hypermethylation of multiple genes in acute myeloid leukemia. Cancer Res. 1999, 59: 3730-3740.PubMed
34.
go back to reference Toyota M, Ahuja N, Ohe-Toyota M, Herman JG, Baylin SB, Issa JP: CpG island methylator phenotype in colorectal cancer. Proc Natl Acad Sci USA. 1999, 96: 8681-8686. 10.1073/pnas.96.15.8681PubMedCentralCrossRefPubMed Toyota M, Ahuja N, Ohe-Toyota M, Herman JG, Baylin SB, Issa JP: CpG island methylator phenotype in colorectal cancer. Proc Natl Acad Sci USA. 1999, 96: 8681-8686. 10.1073/pnas.96.15.8681PubMedCentralCrossRefPubMed
35.
go back to reference Costello JF, Fruhwald MC, Smiraglia DJ, Rush LJ, Robertson GP, Gao X, Wright FA, Feramisco JD, Peltomäki P, Lang JC, Schuller DE, Yu L, Bloomfield CD, Caligiuri MA, Yates A, Nishikawa R, Huang H, Petrelli NJ, Zhang X, O'Dorisio MS, Held WA, Cavenee WK, Plass C: Aberrant CpG-island methylation has non-random and tumour-type-specific patterns. Nat Genet. 2000, 24: 132-138. 10.1038/72785CrossRefPubMed Costello JF, Fruhwald MC, Smiraglia DJ, Rush LJ, Robertson GP, Gao X, Wright FA, Feramisco JD, Peltomäki P, Lang JC, Schuller DE, Yu L, Bloomfield CD, Caligiuri MA, Yates A, Nishikawa R, Huang H, Petrelli NJ, Zhang X, O'Dorisio MS, Held WA, Cavenee WK, Plass C: Aberrant CpG-island methylation has non-random and tumour-type-specific patterns. Nat Genet. 2000, 24: 132-138. 10.1038/72785CrossRefPubMed
36.
go back to reference Suzuki H, Gabrielson E, Chen W, Anbazhagan R, van Engeland M, Weijenberg MP, Herman JG, Baylin SB: A genomic screen for genes upregulated by demethylation and histone deacetylase inhibition in human colorectal cancer. Nat Genet. 2002, 31: 141-149. 10.1038/ng892CrossRefPubMed Suzuki H, Gabrielson E, Chen W, Anbazhagan R, van Engeland M, Weijenberg MP, Herman JG, Baylin SB: A genomic screen for genes upregulated by demethylation and histone deacetylase inhibition in human colorectal cancer. Nat Genet. 2002, 31: 141-149. 10.1038/ng892CrossRefPubMed
37.
go back to reference Shames DS, Girard L, Gao B, Sato M, Lewis CM, Shivapurkar N, Jiang A, Perou CM, Kim YH, Pollack JR, Fong KM, Lam CL, Wong M, Shyr Y, Nanda R, Olopade OI, Gerald W, Euhus DM, Shay JW, Gazdar AF, Minna JD: A genome-wide screen for promoter methylation in lung cancer identifies novel methylation markers for multiple malignancies. PLoS Med. 2006, 3: e486- 10.1371/journal.pmed.0030486PubMedCentralCrossRefPubMed Shames DS, Girard L, Gao B, Sato M, Lewis CM, Shivapurkar N, Jiang A, Perou CM, Kim YH, Pollack JR, Fong KM, Lam CL, Wong M, Shyr Y, Nanda R, Olopade OI, Gerald W, Euhus DM, Shay JW, Gazdar AF, Minna JD: A genome-wide screen for promoter methylation in lung cancer identifies novel methylation markers for multiple malignancies. PLoS Med. 2006, 3: e486- 10.1371/journal.pmed.0030486PubMedCentralCrossRefPubMed
38.
go back to reference Lofton-Day C, Model F, Devos T, Tetzner R, Distler J, Schuster M, Song X, Lesche R, Liebenberg V, Ebert M, Molnar B, Grutzmann R, Pilarsky C, Sledziewski A: DNA methylation biomarkers for blood-based colorectal cancer screening. Clin Chem. 2008, 54: 414-423. 10.1373/clinchem.2007.095992CrossRefPubMed Lofton-Day C, Model F, Devos T, Tetzner R, Distler J, Schuster M, Song X, Lesche R, Liebenberg V, Ebert M, Molnar B, Grutzmann R, Pilarsky C, Sledziewski A: DNA methylation biomarkers for blood-based colorectal cancer screening. Clin Chem. 2008, 54: 414-423. 10.1373/clinchem.2007.095992CrossRefPubMed
39.
go back to reference Zou H, Harrington JJ, Shire AM, Rego RL, Wang L, Campbell ME, Oberg AL, Ahlquist DA: Highly methylated genes in colorectal neoplasia: implications for screening. Cancer Epidemiol Biomarkers Prev. 2007, 16: 2686-2696. 10.1158/1055-9965.EPI-07-0518CrossRefPubMed Zou H, Harrington JJ, Shire AM, Rego RL, Wang L, Campbell ME, Oberg AL, Ahlquist DA: Highly methylated genes in colorectal neoplasia: implications for screening. Cancer Epidemiol Biomarkers Prev. 2007, 16: 2686-2696. 10.1158/1055-9965.EPI-07-0518CrossRefPubMed
40.
go back to reference Weisenberger DJ, Siegmund KD, Campan M, Young J, Long TI, Faasse MA, Kang GH, Widschwendter M, Weener D, Buchanan D, Koh H, Simms L, Barker M, Leggett B, Levine J, Kim M, French AJ, Thibodeau SN, Jass J, Haile R, Laird PW: CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nat Genet. 2006, 38: 787-793. 10.1038/ng1834CrossRefPubMed Weisenberger DJ, Siegmund KD, Campan M, Young J, Long TI, Faasse MA, Kang GH, Widschwendter M, Weener D, Buchanan D, Koh H, Simms L, Barker M, Leggett B, Levine J, Kim M, French AJ, Thibodeau SN, Jass J, Haile R, Laird PW: CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nat Genet. 2006, 38: 787-793. 10.1038/ng1834CrossRefPubMed
41.
go back to reference Chung W, Kwabi-Addo B, Ittmann M, Jelinek J, Shen L, Yu Y, Issa JP: Identification of novel tumor markers in prostate, colon and breast cancer by unbiased methylation profiling. PLoS ONE. 2008, 3: e2079- 10.1371/journal.pone.0002079PubMedCentralCrossRefPubMed Chung W, Kwabi-Addo B, Ittmann M, Jelinek J, Shen L, Yu Y, Issa JP: Identification of novel tumor markers in prostate, colon and breast cancer by unbiased methylation profiling. PLoS ONE. 2008, 3: e2079- 10.1371/journal.pone.0002079PubMedCentralCrossRefPubMed
42.
go back to reference Ausch C, Kim YH, Tsuchiya KD, Dzieciatkowski S, Washington MK, Paraskeva C, Radich J, Grady WM: Comparative analysis of PCR-based biomarker assay methods for colorectal polyp detection from fecal DNA. Clin Chem. 2009, 55: 1559-1563. 10.1373/clinchem.2008.122937CrossRefPubMed Ausch C, Kim YH, Tsuchiya KD, Dzieciatkowski S, Washington MK, Paraskeva C, Radich J, Grady WM: Comparative analysis of PCR-based biomarker assay methods for colorectal polyp detection from fecal DNA. Clin Chem. 2009, 55: 1559-1563. 10.1373/clinchem.2008.122937CrossRefPubMed
43.
go back to reference Kim MS, Chang X, Nagpal JK, Yamashita K, Baek JH, Dasgupta S, Wu G, Osada M, Woo JH, Westra WH, Trink B, Ratovitski EA, Moon C, Sidransky D: The N-methyl-D-aspartate receptor type 2A is frequently methylated in human colorectal carcinoma and suppresses cell growth. Oncogene. 2008, 27: 2045-2054. 10.1038/sj.onc.1210842CrossRefPubMed Kim MS, Chang X, Nagpal JK, Yamashita K, Baek JH, Dasgupta S, Wu G, Osada M, Woo JH, Westra WH, Trink B, Ratovitski EA, Moon C, Sidransky D: The N-methyl-D-aspartate receptor type 2A is frequently methylated in human colorectal carcinoma and suppresses cell growth. Oncogene. 2008, 27: 2045-2054. 10.1038/sj.onc.1210842CrossRefPubMed
44.
45.
go back to reference 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. 2007, 52: 2287-2291. 10.1007/s10620-007-9755-yCrossRefPubMed 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. 2007, 52: 2287-2291. 10.1007/s10620-007-9755-yCrossRefPubMed
46.
go back to reference Oberwalder M, Zitt M, Wöntner C, Fiegl H, Goebel G, Zitt M, Köhle O, Mühlmann G, Öfner D, Margreiter R, Müller HM: SFRP2 methylation in fecal DNA-a marker for colorectal polyps. Int J Colorectal Dis. 2007, 15-9. Oberwalder M, Zitt M, Wöntner C, Fiegl H, Goebel G, Zitt M, Köhle O, Mühlmann G, Öfner D, Margreiter R, Müller HM: SFRP2 methylation in fecal DNA-a marker for colorectal polyps. Int J Colorectal Dis. 2007, 15-9.
47.
go back to reference Wang DR, Tang D: Hypermethylated SFRP2 gene in fecal DNA is a high potential biomarker for colorectal cancer noninvasive screening. World J Gastroenterol. 2008, 14: 524-531. 10.3748/wjg.14.524PubMedCentralCrossRefPubMed Wang DR, Tang D: Hypermethylated SFRP2 gene in fecal DNA is a high potential biomarker for colorectal cancer noninvasive screening. World J Gastroenterol. 2008, 14: 524-531. 10.3748/wjg.14.524PubMedCentralCrossRefPubMed
48.
go back to reference Devos T, Tetzner R, Model F, Weiss G, Schuster M, Distler J, Steiger KV, Grutzmann R, Pilarsky C, Habermann JK, Fleshner PR, Oubre BM, Day R, Sledziewski AZ, Lofton-Day C: Circulating Methylated SEPT9 DNA in Plasma Is a Biomarker for Colorectal Cancer. Clin Chem. 2009 Devos T, Tetzner R, Model F, Weiss G, Schuster M, Distler J, Steiger KV, Grutzmann R, Pilarsky C, Habermann JK, Fleshner PR, Oubre BM, Day R, Sledziewski AZ, Lofton-Day C: Circulating Methylated SEPT9 DNA in Plasma Is a Biomarker for Colorectal Cancer. Clin Chem. 2009
49.
go back to reference Lee B, Godfrey M, Vitale E, Hori H, Mattei MG, Sarfarazi M, Tsipouras P, Ramirez F, Hollister DW: Linkage of Marfan syndrome and a phenotypically related disorder to two different fibrillin genes. Nature. 1991, 352: 330-334. 10.1038/352330a0CrossRefPubMed Lee B, Godfrey M, Vitale E, Hori H, Mattei MG, Sarfarazi M, Tsipouras P, Ramirez F, Hollister DW: Linkage of Marfan syndrome and a phenotypically related disorder to two different fibrillin genes. Nature. 1991, 352: 330-334. 10.1038/352330a0CrossRefPubMed
50.
go back to reference Wang Y, Yu Q, Cho AH, Rondeau G, Welsh J, Adamson E, Mercola D, McClelland M: Survey of differentially methylated promoters in prostate cancer cell lines. Neoplasia. 2005, 7: 748-760. 10.1593/neo.05289PubMedCentralCrossRefPubMed Wang Y, Yu Q, Cho AH, Rondeau G, Welsh J, Adamson E, Mercola D, McClelland M: Survey of differentially methylated promoters in prostate cancer cell lines. Neoplasia. 2005, 7: 748-760. 10.1593/neo.05289PubMedCentralCrossRefPubMed
51.
go back to reference Hellebrekers DM, Melotte V, Vire E, Langenkamp E, Molema G, Fuks F, Herman JG, van Criekinge W, Griffioen AW, van Engeland M: Identification of epigenetically silenced genes in tumor endothelial cells. Cancer Res. 2007, 67: 4138-4148. 10.1158/0008-5472.CAN-06-3032CrossRefPubMed Hellebrekers DM, Melotte V, Vire E, Langenkamp E, Molema G, Fuks F, Herman JG, van Criekinge W, Griffioen AW, van Engeland M: Identification of epigenetically silenced genes in tumor endothelial cells. Cancer Res. 2007, 67: 4138-4148. 10.1158/0008-5472.CAN-06-3032CrossRefPubMed
52.
go back to reference Jowaed A, Schmitt I, Kaut O, Wullner U: Methylation regulates alpha-synuclein expression and is decreased in Parkinson's disease patients' brains. J Neurosci. 2010, 30: 6355-6359. 10.1523/JNEUROSCI.6119-09.2010CrossRefPubMed Jowaed A, Schmitt I, Kaut O, Wullner U: Methylation regulates alpha-synuclein expression and is decreased in Parkinson's disease patients' brains. J Neurosci. 2010, 30: 6355-6359. 10.1523/JNEUROSCI.6119-09.2010CrossRefPubMed
53.
go back to reference Yan PS, Venkataramu C, Ibrahim A, Liu JC, Shen RZ, Diaz NM, Centeno B, Weber F, Leu YW, Shapiro CL, Eng C, Yeatman TJ, Huang TH: Mapping geographic zones of cancer risk with epigenetic biomarkers in normal breast tissue. Clin Cancer Res. 2006, 12: 6626-6636. 10.1158/1078-0432.CCR-06-0467CrossRefPubMed Yan PS, Venkataramu C, Ibrahim A, Liu JC, Shen RZ, Diaz NM, Centeno B, Weber F, Leu YW, Shapiro CL, Eng C, Yeatman TJ, Huang TH: Mapping geographic zones of cancer risk with epigenetic biomarkers in normal breast tissue. Clin Cancer Res. 2006, 12: 6626-6636. 10.1158/1078-0432.CCR-06-0467CrossRefPubMed
54.
go back to reference Lind GE, Danielsen SA, Ahlquist T, Merok MA, Rognum TO, Meling GI, Bretthauer M, Thiis-Evensen E, Nesbakken A, Lothe RA: A novel epigenetic biomarker panel for early detection of colorectal cancer and adenomas. Ejc Supplements. 2009, 7: 145-CrossRef Lind GE, Danielsen SA, Ahlquist T, Merok MA, Rognum TO, Meling GI, Bretthauer M, Thiis-Evensen E, Nesbakken A, Lothe RA: A novel epigenetic biomarker panel for early detection of colorectal cancer and adenomas. Ejc Supplements. 2009, 7: 145-CrossRef
55.
go back to reference Kilpinen S, Autio R, Ojala K, Iljin K, Bucher E, Sara H, Pisto T, Saarela M, Skotheim TI, Bjorkman M, Mpindi JP, Haapa-Paananen S, Vainio P, Edgren H, Wolf M, Astola J, Nees M, Hautaniemi S, Kallioniemi O: Systematic bioinformatic analysis of expression levels of 17, 330 human genes across 9, 783 samples from 175 types of healthy and pathological tissues. Genome Biol. 2008, 9: R139- 10.1186/gb-2008-9-9-r139PubMedCentralCrossRefPubMed Kilpinen S, Autio R, Ojala K, Iljin K, Bucher E, Sara H, Pisto T, Saarela M, Skotheim TI, Bjorkman M, Mpindi JP, Haapa-Paananen S, Vainio P, Edgren H, Wolf M, Astola J, Nees M, Hautaniemi S, Kallioniemi O: Systematic bioinformatic analysis of expression levels of 17, 330 human genes across 9, 783 samples from 175 types of healthy and pathological tissues. Genome Biol. 2008, 9: R139- 10.1186/gb-2008-9-9-r139PubMedCentralCrossRefPubMed
Metadata
Title
Identification of an epigenetic biomarker panel with high sensitivity and specificity for colorectal cancer and adenomas
Authors
Guro E Lind
Stine A Danielsen
Terje Ahlquist
Marianne A Merok
Kim Andresen
Rolf I Skotheim
Merete Hektoen
Torleiv O Rognum
Gunn I Meling
Geir Hoff
Michael Bretthauer
Espen Thiis-Evensen
Arild Nesbakken
Ragnhild A Lothe
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2011
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-10-85

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