Skip to main content

Advertisement

Log in

TWIST1 Promoter Methylation in Primary Colorectal Carcinoma

  • Research
  • Published:
Pathology & Oncology Research

Abstract

TWIST1 gene, a transcription factor that belongs to the family of basic helix–loop–helix proteins, has been related to tumor progression and metastasis in different cancers. The aim of our study was to investigate TWIST1 promoter methylation in patients with primary colorectal carcinoma and determine its correlation with prognostic factors and disease outcome. Seventy-three patients with primary colorectal adenocarcinoma were studied. From each patient two tissue samples were collected: one sample of the tumor and one sample of normal colorectal tissue from an area located 15 cm away from the tumor. Samples of colorectal mucosa obtained from 30 individuals without malignant disease were also studied as a control group. All tissues were analyzed through methylation-specific PCR. TWIST1 hypermethylation was detected in colorectal specimens of 46 patients with cancer, but in none of the tissues from the nonmalignant control group (p < 0.001). In cancer patients, TWIST1 hypermethylation was found in 38 of 73 tumor samples as compared with 20 of 73 matched samples of non-cancerous colorectal tissue (P = 0.001). TWIST1 hypermethylation was not correlated with prognostic predictors for the disease outcome, patients’ overall survival and disease-free survival rates. We concluded that TWIST1 hypermethylation is present in the colon and rectum of most patients with colorectal carcinoma, suggesting this molecular alteration may be involved in the process of colorectal carcinogenesis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Issa JP (2000) The epigenetics of colorectal cancer. Ann N Y Acad Sci 910:140–153

    Article  PubMed  CAS  Google Scholar 

  2. Lee S, Hwang KS, Lee HJ et al (2004) Aberrant CpG island hypermethylation of multiple genes in colorectal neoplasia. Lab Invest 84:884–893

    Article  PubMed  CAS  Google Scholar 

  3. Toyota M, Ahuja N, Ohe-Toyota M et al (1999) CpG island methylator phenotype in colorectal cancer. Proc Natl Acad Sci U S A 96:8681–8686

    Article  PubMed  CAS  Google Scholar 

  4. Weisenberger DJ, Siegmund KD, Campan M et al (2006) CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nat Genet 38:787–793

    Article  PubMed  CAS  Google Scholar 

  5. Teodoridis JM, Hardie C, Brown R (2008) CpG island methylator phenotype (CIMP) in cancer: causes and implications. Cancer Lett 268:177–186

    Article  PubMed  CAS  Google Scholar 

  6. Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61:759–767

    Article  PubMed  CAS  Google Scholar 

  7. Feinberg AP, Ohlsson R, Henikoff S (2006) The epigenetic progenitor origin of human cancer. Nat Rev Genet 7:21–33

    Article  PubMed  CAS  Google Scholar 

  8. Fackler MJ, McVeigh M, Evron E et al (2003) DNA methylation of RASSF1A, HIN-1, RAR-beta, Cyclin D2 and TWIST in situ and invasive lobular breast carcinoma. Int J Cancer 107:970–975

    Article  PubMed  CAS  Google Scholar 

  9. Gort EH, Suijkerbuijk KP, Roothaan SM et al (2008) Methylation of the TWIST1 promoter, TWIST1 mRNA levels, and immunohistochemical expression of TWIST1 in breast cancer. Cancer Epidemiol Biomarkers Prev 17:3325–3330

    Article  PubMed  CAS  Google Scholar 

  10. Kwok WK, Ling MT, Lee TW et al (2005) Up-regulation of TWIST in prostate cancer and its implication as a therapeutic target. Cancer Res 65:5153–5162

    Article  PubMed  CAS  Google Scholar 

  11. Füchtbauer EM (1995) Expression of M-TWIST during postimplantation development of the mouse. Dev Dyn 204:316–322

    Article  PubMed  Google Scholar 

  12. Maestro R, Dei Tos AP, Hamamori Y et al (1999) TWIST is a potential oncogene that inhibits apoptosis. Genes Dev 13:2207–2217

    Article  PubMed  CAS  Google Scholar 

  13. Mironchik Y, Winnard PT Jr, Vesuna F et al (2005) TWIST1 overexpression induces in vivo angiogenesis and correlates with chromosomal instability in breast cancer. Cancer Res 65:10801–10809

    Article  PubMed  CAS  Google Scholar 

  14. Elias MC, Tozer KR, Silber JR et al (2005) TWIST1 is expressed in human gliomas and promotes invasion. Neoplasia 7:824–837

    Article  PubMed  CAS  Google Scholar 

  15. Valdés-Mora F, Gómez del Pulgar T, Bandrés E et al (2009) TWIST1 overexpression is associated with nodal invasion and male sex in primary colorectal cancer. Ann Surg Oncol 16:78–87

    Article  PubMed  Google Scholar 

  16. Kyo S, Sakaguchi J, Ohno S et al (2006) High TWIST1 expression is involved in infiltrative endometrial cancer and affects patient survival. Hum Pathol 37:431–438

    Article  PubMed  CAS  Google Scholar 

  17. Vesuna F, van Diest P, Chen JH, Raman V (2008) Twist is a transcriptional repressor of E-cadherin gene expression in breast cancer. Biochem Biophys Res Commun 367:235–241

    Article  PubMed  CAS  Google Scholar 

  18. Rosivatz E, Becker I, Specht K et al (2002) Differential expression of the epithelial-mesenchymal transition regulators snail, SIP1, and TWIST1 in gastric cancer. Am J Pathol 161:1881–1891

    Article  PubMed  CAS  Google Scholar 

  19. Yan-Qi Z, Xue-Yan G, Shuang H et al (2007) Expression and significance of TWIST basic helix-loop-helix protein over-expression in gastric cancer. Pathology 39:470–475

    Article  PubMed  Google Scholar 

  20. Yuen HF, Chan YP, Wong ML et al (2007) Upregulation of Twist in oesophageal squamous cell carcinoma is associated with neoplastic transformation and distant metastasis. J Clin Pathol 60:510–514

    Article  PubMed  CAS  Google Scholar 

  21. Ohuchida K, Mizumoto K, Ohhashi S et al (2007) Twist, a novel oncogene, is upregulated in pancreatic cancer: clinical implication of Twist expression in pancreatic juice. Int J Cancer 120:1634–1640

    Article  PubMed  CAS  Google Scholar 

  22. American Joint Committee on Cancer (AJCC) (1988) Manual for staging of cancer, 3rd edn. Lippincott, Philadelphia

    Google Scholar 

  23. 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 U S A 93:9821–9826

    Article  PubMed  CAS  Google Scholar 

  24. Leslie A, Carey FA, Pratt NR, Steele RJ (2002) The colorectal adenoma-carcinoma sequence. Br J Surg 89:845–860

    Article  PubMed  CAS  Google Scholar 

  25. Peltomäki P (2001) Deficient DNA mismatch repair: a common etiologic factor for colon cancer. Hum Mol Genet 10:735–740

    Article  PubMed  Google Scholar 

  26. Baylin SB, Ohm JE (2006) Epigenetic gene silencing in cancer - a mechanism for early oncogenic pathway addiction? Nat Rev Cancer 6:107–116

    Article  PubMed  CAS  Google Scholar 

  27. Frigola J, Solé X, Paz MF et al (2005) Differential DNA hypermethylation and hypomethylation signatures in colorectal cancer. Hum Mol Genet 14:319–326

    Article  PubMed  CAS  Google Scholar 

  28. Yang J, Mani SA, Donaher JL et al (2004) TWIST1, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 117:927–939

    Article  PubMed  CAS  Google Scholar 

  29. Yang J, Mani SA, Weinberg RA (2006) Exploring a new TWIST1 on tumor metastasis. Cancer Res 66:4549–4552

    Article  PubMed  CAS  Google Scholar 

  30. Okada T, Suheiro Y, Ueno K et al (2010) TWIST1 hypermethylation is observed frequently in colorectal tumors and its overexpression is associated with unfavorable outcomes in patients with colorectal cancer. Genes Chromosomes Cancer 49:452–462

    PubMed  CAS  Google Scholar 

  31. Martin TA, Goyal A, Watkins G, Jiang WG (2005) Expression of the transcription factors snail, slug, and TWIST1 and their clinical significance in human breast cancer. Ann Surg Oncol 12:488–496

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Daniel C. Damin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ruppenthal, R.D., Nicolini, C., Filho, A.F.F. et al. TWIST1 Promoter Methylation in Primary Colorectal Carcinoma. Pathol. Oncol. Res. 17, 867–872 (2011). https://doi.org/10.1007/s12253-011-9395-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12253-011-9395-6

Keywords

Navigation