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Epigenetic Regulation of WNT Signaling Pathway Genes in Inflammatory Bowel Disease (IBD) Associated Neoplasia

  • ssat plenary presentation
  • Published:
Journal of Gastrointestinal Surgery Aims and scope

Abstract

Introduction

WNT signaling pathway dysregulation is an important event in the pathogenesis of colorectal cancer (CRC) with APC mutations seen in more than 80% of sporadic CRC. However, such mutations in the WNT signaling pathway genes are rare in inflammatory bowel disease (IBD) associated neoplasia (dysplasia and cancer). This study examined the role of epigenetic silencing of WNT signaling pathway genes in the pathogenesis of IBD-associated neoplasia.

Methods

Paraffin-embedded tissue samples were obtained and methylation of ten WNT signaling pathway genes, including APC1A, APC2, SFRP1, SFRP2, SFRP4, SFRP5, DKK1, DKK3, WIF1 and LKB1, was analyzed. Methylation analysis was performed on 41 IBD samples, 27 normal colon samples (NCs), and 24 sporadic CRC samples.

Results

Methylation of WNT signaling pathway genes is a frequent and early event in IBD and IBD-associated neoplasia. A progressive increase in the percentage of methylated genes in the WNT signaling pathway from NCs (4.2%) to IBD colitis (39.7%) to IBD-associated neoplasia (63.4%) was seen (NCs vs. IBD colitis, p < 0.01; IBD colitis vs. IBD-associated neoplasia, p = 0.01). In the univariate logistic regression model, methylation of APC2 (OR 4.7, 95% CI: 1.1–20.63, p = 0.04), SFRP1 (OR 5.1, 95% CI: 1.1–31.9, p = 0.04), and SFRP2 (OR 5.1, 95% CI: 1.1–32.3, p = 0.04) was associated with progression from IBD colitis to IBD-associated neoplasia, while APC1A methylation was borderline significant (OR 4.1, 95% CI: 0.95–17.5, p = 0.06). In the multivariate logistic regression model, methylation of APC1A and APC2 was more likely to be associated with IBD-associated neoplasia than IBD colitis. (OR APC1A: 6.4, 95% CI: 1.1–37.7 p = 0.04; OR APC2 9.1, 95% CI: 1.3–61.7, p = 0.02).

Summary

Methylation of the WNT signaling genes is an early event seen in patients with IBD colitis and there is a progressive increase in methylation of the WNT signaling genes during development of IBD-associated neoplasia. Moreover, methylation of APC1A, APC2, SFRP1, and SFRP2 appears to mark progression from IBD colitis to IBD-associated neoplasia, and these genes may serve as biomarkers for IBD-associated neoplasia.

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References

  1. Hanauer SB. Inflammatory bowel disease: epidemiology, pathogenesis, and therapeutic opportunities. Inflamm Bowel Dis 2006;12(Suppl 1):S3–S9. doi:10.1097/01.MIB.0000195385.19268.68.

    Article  PubMed  Google Scholar 

  2. Ekbom A, Helmick C, Zack M, Adami HO. Ulcerative colitis and colorectal cancer. A population-based study. N Engl J Med 1990;323(18):1228–1233.

    PubMed  CAS  Google Scholar 

  3. Ekbom A, Helmick C, Zack M, Adami HO. Increased risk of large-bowel cancer in Crohn’s disease with colonic involvement. Lancet 1990;336(8711):357–359. doi:10.1016/0140-6736(90)91889-I.

    Article  PubMed  CAS  Google Scholar 

  4. Langholz E, Munkholm P, Davidsen M, Binder V. Colorectal cancer risk and mortality in patients with ulcerative colitis. Gastroenterology 1992;103(5):1444–1451.

    PubMed  CAS  Google Scholar 

  5. Greenstein AJ, Sachar DB, Smith H, Pucillo A, Papatestas AE, Kreel I, et al. Cancer in universal and left-sided ulcerative colitis: factors determining risk. Gastroenterology 1979;77(2):290–294.

    PubMed  CAS  Google Scholar 

  6. Harpaz N, Talbot IC. Colorectal cancer in idiopathic inflammatory bowel disease. Semin Diagn Pathol 1996;13(4):339–357.

    PubMed  CAS  Google Scholar 

  7. Eaden JA, Abrams KR, Mayberry JF. The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut 2001;48(4):526–535. doi:10.1136/gut.48.4.526.

    Article  PubMed  CAS  Google Scholar 

  8. Rutter MD, Saunders BP, Wilkinson KH, Rumbles S, Schofield G, Kamm MA, et al. Thirty-year analysis of a colonoscopic surveillance program for neoplasia in ulcerative colitis. Gastroenterology 2006;130(4):1030–1038. doi:10.1053/j.gastro.2005.12.035.

    Article  PubMed  Google Scholar 

  9. Farrell RJ, Peppercorn MA. Ulcerative colitis. Lancet 2002;359(9303):331–340. doi:10.1016/S0140-6736(02)07499-8.

    Article  PubMed  Google Scholar 

  10. Hata K, Watanabe T, Kazama S, Suzuki K, Shinozaki M, Yokoyama T, et al. Earlier surveillance colonoscopy programme improves survival in patients with ulcerative colitis associated colorectal cancer: results of a 23-year surveillance programme in the Japanese population. Br J Cancer 2003;89(7):1232–1236. doi:10.1038/sj.bjc.6601247.

    Article  PubMed  CAS  Google Scholar 

  11. Karlen P, Kornfeld D, Brostrom O, Lofberg R, Persson PG, Ekbom A. Is colonoscopic surveillance reducing colorectal cancer mortality in ulcerative colitis? A population based case control study. Gut 1998;42(5):711–714.

    PubMed  CAS  Google Scholar 

  12. Woolrich AJ, DaSilva MD, Korelitz BI. Surveillance in the routine management of ulcerative colitis: the predictive value of low-grade dysplasia. Gastroenterology 1992;103(2):431–438.

    PubMed  CAS  Google Scholar 

  13. Chambers WM, Warren BF, Jewell DP, Mortensen NJ. Cancer surveillance in ulcerative colitis. Br J Surg 2005;92(8):928–936. doi:10.1002/bjs.5106.

    Article  PubMed  CAS  Google Scholar 

  14. Ullman TA. Preventing neoplastic progression in ulcerative colitis. J Clin Gastroenterol 2005;39(4Suppl 2):S66–S69. doi:10.1097/01.mcg.0000155554.01336.ff.

    Article  PubMed  Google Scholar 

  15. Rubin CE, Haggitt RC, Burmer GC, Brentnall TA, Stevens AC, Levine DS, et al. DNA aneuploidy in colonic biopsies predicts future development of dysplasia in ulcerative colitis. Gastroenterology 1992;103(5):1611–1620.

    PubMed  CAS  Google Scholar 

  16. Axon AT. Colonic cancer surveillance in ulcerative colitis is not essential for every patient. Eur J Cancer 1995;31A(7–8):1183–1186. doi:10.1016/0959-8049(95)00131-2.

    Article  PubMed  CAS  Google Scholar 

  17. Choi PM, Nugent FW, Schoetz DJ Jr, Silverman ML, Haggitt RC. Colonoscopic surveillance reduces mortality from colorectal cancer in ulcerative colitis. Gastroenterology 1993;105(2):418–424.

    PubMed  CAS  Google Scholar 

  18. Lynch DA, Lobo AJ, Sobala GM, Dixon MF, Axon AT. Failure of colonoscopic surveillance in ulcerative colitis. Gut 1993;34(8):1075–1080. doi:10.1136/gut.34.8.1075.

    Article  PubMed  CAS  Google Scholar 

  19. Baylin SB, Herman JG. DNA hypermethylation in tumorigenesis: epigenetics joins genetics. Trends Genet 2000;16(4):168–174. doi:10.1016/S0168-9525(99)01971-X.

    Article  PubMed  CAS  Google Scholar 

  20. Baylin SB. DNA methylation and gene silencing in cancer. Nat Clin Pract Oncol 2005;2(Suppl 1):S4–S11. doi:10.1038/ncponc0354.

    Article  PubMed  CAS  Google Scholar 

  21. Herman JG, Baylin SB. Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med 2003;349(21):2042–2054. doi:10.1056/NEJMra023075.

    Article  PubMed  CAS  Google Scholar 

  22. Azarschab P, Porschen R, Gregor M, Blin N, Holzmann K. Epigenetic control of the E-cadherin gene (CDH1) by CpG methylation in colectomy samples of patients with ulcerative colitis. Genes Chromosomes Cancer 2002;35(2):121–126. doi:10.1002/gcc.10101.

    Article  PubMed  CAS  Google Scholar 

  23. Fleisher AS, Esteller M, Harpaz N, Leytin A, Rashid A, Xu Y, et al. Microsatellite instability in inflammatory bowel disease-associated neoplastic lesions is associated with hypermethylation and diminished expression of the DNA mismatch repair gene, hMLH1. Cancer Res 2000;60(17):4864–4868.

    PubMed  CAS  Google Scholar 

  24. Hsieh CJ, Klump B, Holzmann K, Borchard F, Gregor M, Porschen R. Hypermethylation of the p16INK4a promoter in colectomy specimens of patients with long-standing and extensive ulcerative colitis. Cancer Res 1998;58(17):3942–3945.

    PubMed  CAS  Google Scholar 

  25. Issa JP, Ahuja N, Toyota M, Bronner MP, Brentnall TA. Accelerated age-related CpG island methylation in ulcerative colitis. Cancer Res 2001;61(9):3573–3577.

    PubMed  CAS  Google Scholar 

  26. Moriyama T, Matsumoto T, Nakamura S, Jo Y, Mibu R, Yao T, et al. Hypermethylation of p14 (ARF) may be predictive of colitic cancer in patients with ulcerative colitis. Dis Colon Rectum 2007;50(9):1384–1392. doi:10.1007/10350-007-0302-x.

    Article  PubMed  Google Scholar 

  27. de Lau W, Barker N, Clevers H. WNT signaling in the normal intestine and colorectal cancer. Front Biosci 2007;12:471–491. doi:10.2741/2076.

    Article  PubMed  Google Scholar 

  28. Pinto D, Clevers H. Wnt control of stem cells and differentiation in the intestinal epithelium. Exp Cell Res 2005;306(2):357–363. doi:10.1016/j.yexcr.2005.02.022.

    Article  PubMed  CAS  Google Scholar 

  29. Miyoshi Y, Nagase H, Ando H, Horii A, Ichii S, Nakatsuru S, et al. Somatic mutations of the APC gene in colorectal tumors: mutation cluster region in the APC gene. Hum Mol Genet 1992;1(4):229–233. doi:10.1093/hmg/1.4.229.

    Article  PubMed  CAS  Google Scholar 

  30. Potter JD. Colorectal cancer: molecules and populations. J Natl Cancer Inst 1999;91(11):916–932. doi:10.1093/jnci/91.11.916.

    Article  PubMed  CAS  Google Scholar 

  31. Cadigan KM, Nusse R. Wnt signaling: a common theme in animal development. Genes Dev 1997;11(24):3286–3305. doi:10.1101/gad.11.24.3286.

    Article  PubMed  CAS  Google Scholar 

  32. Klingensmith J, Nusse R, Perrimon N. The Drosophila segment polarity gene dishevelled encodes a novel protein required for response to the wingless signal. Genes Dev 1994;8(1):118–130. doi:10.1101/gad.8.1.118.

    Article  PubMed  CAS  Google Scholar 

  33. Behrens J, von Kries JP, Kuhl M, Bruhn L, Wedlich D, Grosschedl R, et al. Functional interaction of beta-catenin with the transcription factor LEF-1. Nature 1996;382(6592):638–642. doi:10.1038/382638a0.

    Article  PubMed  CAS  Google Scholar 

  34. He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, et al. Identification of c-MYC as a target of the APC pathway. Science 1998;281(5382):1509–1512. doi:10.1126/science.281.5382.1509.

    Article  PubMed  CAS  Google Scholar 

  35. Howe LR, Subbaramaiah K, Chung WJ, Dannenberg AJ, Brown AM. Transcriptional activation of cyclooxygenase-2 in Wnt-1-transformed mouse mammary epithelial cells. Cancer Res 1999;59(7):1572–1577.

    PubMed  CAS  Google Scholar 

  36. Shtutman M, Zhurinsky J, Simcha I, Albanese C, D’Amico M, Pestell R, et al. The cyclin D1 gene is a target of the beta-catenin/LEF-1 pathway. Proc Natl Acad Sci USA 1999;96(10):5522–5527. doi:10.1073/pnas.96.10.5522.

    Article  PubMed  CAS  Google Scholar 

  37. Bafico A, Gazit A, Pramila T, Finch PW, Yaniv A, Aaronson SA. Interaction of frizzled related protein (FRP) with Wnt ligands and the frizzled receptor suggests alternative mechanisms for FRP inhibition of Wnt signaling. J Biol Chem 1999;274(23):16180–16187. doi:10.1074/jbc.274.23.16180.

    Article  PubMed  CAS  Google Scholar 

  38. Zorn AM. Wnt signalling: antagonistic Dickkopfs. Curr Biol 2001;11(15):R592–R595. doi:10.1016/S0960-9822(01)00360-8.

    Article  PubMed  CAS  Google Scholar 

  39. Tarmin L, Yin J, Harpaz N, Kozam M, Noordzij J, Antonio LB, et al. Adenomatous polyposis coli gene mutations in ulcerative colitis-associated dysplasias and cancers versus sporadic colon neoplasms. Cancer Res 1995;55(10):2035–2038.

    PubMed  CAS  Google Scholar 

  40. You J, Nguyen AV, Albers CG, Lin F, Holcombe RF. Wnt pathway-related gene expression in inflammatory bowel disease. Dig Dis Sci 2008;53(4):1013–1019. doi:10.1007/s10620-007-9973-3.

    Article  PubMed  CAS  Google Scholar 

  41. You XJ, Bryant PJ, Jurnak F, Holcombe RF. Expression of Wnt pathway components frizzled and disheveled in colon cancer arising in patients with inflammatory bowel disease. Oncol Rep 2007;18(3):691–694.

    PubMed  Google Scholar 

  42. van Dekken H, Wink JC, Vissers KJ, Franken PF, Ruud Schouten W, Hop WCJ, Kuipers EJ, Fodde R, Janneke van der Woude C. Wnt pathway-related gene expression during malignant progression in ulcerative colitis. Acta Histochem 2007;109(4):266–272. doi:10.1016/j.acthis.2007.02.007.

    Article  PubMed  CAS  Google Scholar 

  43. Aust DE, Terdiman JP, Willenbucher RF, Chang CG, Molinaro-Clark A, Baretton GB, et al. The APC/beta-catenin pathway in ulcerative colitis-related colorectal carcinomas: a mutational analysis. Cancer 2002;94(5):1421–1427. doi:10.1002/cncr.10334.

    Article  PubMed  CAS  Google Scholar 

  44. Aust DE, Terdiman JP, Willenbucher RF, Chew K, Ferrell L, Florendo C, et al. Altered distribution of beta-catenin, and its binding proteins E-cadherin and APC, in ulcerative colitis-related colorectal cancers. Mod Pathol 2001;14(1):29–39. doi:10.1038/modpathol.3880253.

    Article  PubMed  CAS  Google Scholar 

  45. Herman JG, Graff JR, Myohanen S, Nelkin BD, Baylin SB. Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci USA 1996;93(18):9821–9826. doi:10.1073/pnas.93.18.9821.

    Article  PubMed  CAS  Google Scholar 

  46. Rhee I, Bachman KE, Park BH, Jair KW, Yen RW, Schuebel KE, et al. DNMT1 and DNMT3b cooperate to silence genes in human cancer cells. Nature 2002;416(6880):552–556. doi:10.1038/416552a.

    Article  PubMed  CAS  Google Scholar 

  47. Arnold CN, Goel A, Niedzwiecki D, Dowell JM, Wasserman L, Compton C, et al. APC promoter hypermethylation contributes to the loss of APC expression in colorectal cancers with allelic loss on 5q. Cancer Biol Ther 2004;3(10):960–964.

    Article  PubMed  CAS  Google Scholar 

  48. Suzuki H, Watkins DN, Jair KW, Schuebel KE, Markowitz SD, Chen WD, et al. Epigenetic inactivation of SFRP genes allows constitutive WNT signaling in colorectal cancer. Nat Genet 2004;36(4):417–422. doi:10.1038/ng1330.

    Article  PubMed  CAS  Google Scholar 

  49. Aguilera O, Fraga MF, Ballestar E, Paz MF, Herranz M, Espada J, et al. Epigenetic inactivation of the Wnt antagonist DICKKOPF-1 (DKK-1) gene in human colorectal cancer. Oncogene 2006;25(29):4116–4121. doi:10.1038/sj.onc.1209439.

    Article  PubMed  CAS  Google Scholar 

  50. Taniguchi H, Yamamoto H, Hirata T, Miyamoto N, Oki M, Nosho K, et al. Frequent epigenetic inactivation of Wnt inhibitory factor-1 in human gastrointestinal cancers. Oncogene 2005;24(53):7946–7952. doi:10.1038/sj.onc.1208910.

    Article  PubMed  CAS  Google Scholar 

  51. Schuebel KE, Chen W, Cope L, Glockner SC, Suzuki H, Yi JM, et al. Comparing the DNA hypermethylome with gene mutations in human colorectal cancer. PLoS Genet 2007;3(9):1709–1723. doi:10.1371/journal.pgen.0030157.

    Article  PubMed  CAS  Google Scholar 

  52. Wang FY, Arisawa T, Tahara T, Takahama K, Watanabe M, Hirata I, et al. Aberrant DNA methylation in ulcerative colitis without neoplasia. Hepatogastroenterology 2008;55(81):62–65.

    PubMed  CAS  Google Scholar 

  53. Eads CA, Lord RV, Kurumboor SK, Wickramasinghe K, Skinner ML, Long TI, et al. Fields of aberrant CpG island hypermethylation in Barrett’s esophagus and associated adenocarcinoma. Cancer Res 2000;60(18):5021–5026.

    PubMed  CAS  Google Scholar 

  54. Tamura G, Yin J, Wang S, Fleisher AS, Zou T, Abraham JM, et al. E-Cadherin gene promoter hypermethylation in primary human gastric carcinomas. J Natl Cancer Inst 2000;92(7):569–573. doi:10.1093/jnci/92.7.569.

    Article  PubMed  CAS  Google Scholar 

  55. Okochi O, Hibi K, Sakai M, Inoue S, Takeda S, Kaneko T, et al. Methylation-mediated silencing of SOCS-1 gene in hepatocellular carcinoma derived from cirrhosis. Clin Cancer Res 2003;9(14):5295–5298.

    PubMed  CAS  Google Scholar 

  56. Collins RH Jr, Feldman M, Fordtran JS. Colon cancer, dysplasia, and surveillance in patients with ulcerative colitis. A critical review. N Engl J Med 1987;316(26):1654–1658.

    PubMed  Google Scholar 

  57. Connell WR, Lennard-Jones JE, Williams CB, Talbot IC, Price AB, Wilkinson KH. Factors affecting the outcome of endoscopic surveillance for cancer in ulcerative colitis. Gastroenterology 1994;107(4):934–944.

    PubMed  CAS  Google Scholar 

  58. Melville DM, Jass JR, Morson BC, Pollock DJ, Richman PI, Shepherd NA, et al. Observer study of the grading of dysplasia in ulcerative colitis: comparison with clinical outcome. Hum Pathol 1989;20(10):1008–1014. doi:10.1016/0046-8177(89)90273-6.

    Article  PubMed  CAS  Google Scholar 

  59. Dixon MF, Brown LJ, Gilmour HM, Price AB, Smeeton NC, Talbot IC, et al. Observer variation in the assessment of dysplasia in ulcerative colitis. Histopathology 1988;13(4):385–397. doi:10.1111/j.1365-2559.1988.tb02055.x.

    Article  PubMed  CAS  Google Scholar 

  60. Riddell RH, Goldman H, Ransohoff DF, Appelman HD, Fenoglio CM, Haggitt RC, et al. Dysplasia in inflammatory bowel disease: standardized classification with provisional clinical applications. Hum Pathol 1983;14(11):931–968. doi:10.1016/S0046-8177(83)80175-0.

    Article  PubMed  CAS  Google Scholar 

  61. Rubin DT, Kavitt RT. Surveillance for cancer and dysplasia in inflammatory bowel disease. Gastroenterol Clin North Am 2006;35(3):581–604. doi:10.1016/j.gtc.2006.07.001.

    Article  PubMed  Google Scholar 

  62. Kern SE, Redston M, Seymour AB, Caldas C, Powell SM, Kornacki S, et al. Molecular genetic profiles of colitis-associated neoplasms. Gastroenterology 1994;107(2):420–428.

    PubMed  CAS  Google Scholar 

  63. Nakagawa H, Murata Y, Koyama K, Fujiyama A, Miyoshi Y, Monden M, et al. Identification of a brain-specific APC homologue, APCL, and its interaction with beta-catenin. Cancer Res 1998;58(22):5176–5181.

    PubMed  CAS  Google Scholar 

  64. van Es JH, Kirkpatrick C, van de Wetering M, Molenaar M, Miles A, Kuipers J, et al. Identification of APC2, a homologue of the adenomatous polyposis coli tumour suppressor. Curr Biol 1999;9(2):105–108. doi:10.1016/S0960-9822(99)80024-4.

    Article  PubMed  Google Scholar 

  65. Brentnall TA, Crispin DA, Rabinovitch PS, Haggitt RC, Rubin CE, Stevens AC, et al. Mutations in the p53 gene: an early marker of neoplastic progression in ulcerative colitis. Gastroenterology 1994;107(2):369–378.

    PubMed  CAS  Google Scholar 

  66. Burmer GC, Rabinovitch PS, Haggitt RC, Crispin DA, Brentnall TA, Kolli VR, et al. Neoplastic progression in ulcerative colitis: histology, DNA content, and loss of a p53 allele. Gastroenterology 1992;103(5):1602–1610.

    PubMed  CAS  Google Scholar 

  67. Nakagawa H, Koyama K, Murata Y, Morito M, Akiyama T, Nakamura Y. APCL, a central nervous system-specific homologue of adenomatous polyposis coli tumor suppressor, binds to p53-binding protein 2 and translocates it to the perinucleus. Cancer Res 2000;60(1):101–105.

    PubMed  CAS  Google Scholar 

  68. Yin J, Harpaz N, Tong Y, Huang Y, Laurin J, Greenwald BD, et al. p53 point mutations in dysplastic and cancerous ulcerative colitis lesions. Gastroenterology 1993;104(6):1633–1639.

    PubMed  CAS  Google Scholar 

  69. Bronner MP, Culin C, Reed JC, Furth EE. The bcl-2 proto-oncogene and the gastrointestinal epithelial tumor progression model. Am J Pathol 1995;146(1):20–26.

    PubMed  CAS  Google Scholar 

  70. Kawano Y, Kypta R. Secreted antagonists of the Wnt signalling pathway. J Cell Sci 2003;116(Pt 13):2627–2634. doi:10.1242/jcs.00623.

    Article  PubMed  CAS  Google Scholar 

  71. Levin B, Lieberman DA, McFarland B, Andrews KS, Brooks D, Dash C, et al. 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. Cancer J Clin 2008;58:130–160.

    Article  Google Scholar 

  72. Zhang W, Bauer M, Croner RS, Pelz JO, Lodygin D, Hermeking H, et al. DNA stool test for colorectal cancer: hypermethylation of the secreted frizzled-related protein-1 gene. Dis Colon Rectum 2007;50(10):1618–1626, 1626–1617. discussion, doi:10.1007/s10350-007-0286-6.

    Article  PubMed  Google Scholar 

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Acknowledgments

We thank Marco A. Riojas for technical assistance.

NA is supported by the American Surgical Association Fellowship Award, Wendy Will Cancer Fund, and the Richard Ross Clinician Scientist Award.

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Authors and Affiliations

  1. Department of Surgery, Johns Hopkins University, Baltimore, MD, 21231, USA

    Mashaal Dhir, Sabine C. Glöckner, Susan L. Gearhart & Nita Ahuja

  2. Department of Pathology, Johns Hopkins University, Baltimore, MD, 21231, USA

    Elizabeth A. Montgomery

  3. Department of Oncology, Johns Hopkins University, Baltimore, MD, 21231, USA

    Kornel E. Schuebel, Craig M. Hooker, James G. Herman, Stephen B. Baylin & Nita Ahuja

  4. Blalock 658, 600 N Wolfe St, Baltimore, MD, 21287, USA

    Susan L. Gearhart

  5. 1650 Orleans Street, CRB 1 Room 342, Baltimore, MD, 21287, USA

    Nita Ahuja

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  1. Mashaal Dhir
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Correspondence to Susan L. Gearhart or Nita Ahuja.

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Dhir, M., Montgomery, E.A., Glöckner, S.C. et al. Epigenetic Regulation of WNT Signaling Pathway Genes in Inflammatory Bowel Disease (IBD) Associated Neoplasia. J Gastrointest Surg 12, 1745–1753 (2008). https://doi.org/10.1007/s11605-008-0633-5

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