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Epigenetic Characterization of Cell-Free DNA

  • Giorgia GurioliEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1909)

Abstract

Cell-free DNA can be evaluated for the epigenetic component. Epigenetic alterations consist of changes in gene functions that do not involve changes in DNA sequence. The mainly studied epigenetic alteration is DNA methylation occurring at CpG islands in the promoter regions for which several literature data showed clinical relevance. This chapter is an overview of the epigenetic alterations detected in cell-free DNA.

Key words

Cell-free DNA Epigenetic alterations DNA methylation Plasma Serum Urine 

References

  1. 1.
    Breitbach S, Tug S, Simon P (2012) Circulating cell-free DNA an up-coming molecular marker in exercise physiology. Sports Med 42:565–586CrossRefGoogle Scholar
  2. 2.
    Schwarzenbach H, Hoon DS, Pantel K (2011) Cell-free nucleic acids as biomarkers in cancer patients. Nat Rev Cancer 11:426–437CrossRefGoogle Scholar
  3. 3.
    Sirchia SM, Ramoscelli L, Grati FR et al (2005) Loss of the inactive X chromosome and replication of the active X in BRCA1-defective and wild-type breast cancer cells. Cancer Res 65(6):2139–2146CrossRefGoogle Scholar
  4. 4.
    Rodriguez J, Munoz M, Vives L et al (2008) Bivalent domains enforce transcriptional memory of DNA methylated genes in cancer cells. Proc Natl Acad Sci U S A 105(50):19809–19814CrossRefGoogle Scholar
  5. 5.
    Sirchia SM, Miozzo M (2012) Significance of clustered tumor suppressor genes in cancer. Future Oncol 8(9):1091–1093CrossRefGoogle Scholar
  6. 6.
    Mikeska T, Craig JM (2014) DNA methylation biomarkers: cancer and beyond. Genes (Basel) 5(3):821–864CrossRefGoogle Scholar
  7. 7.
    Lister R, Pelizzola M, Dowen RH et al (2009) Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 462(7271):315–322CrossRefGoogle Scholar
  8. 8.
    Portela A, Esteller M (2010) Epigenetic modifications and human disease. Nat Biotechnol 28(10):1057–1068CrossRefGoogle Scholar
  9. 9.
    Berdasco M, Esteller M (2010) Aberrant epigenetic landscape in cancer: how cellular identity goes awry. Dev Cell 19(5):698–711CrossRefGoogle Scholar
  10. 10.
    Xu W, Yang H, Liu Y et al (2011) Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases. Cancer Cell 19(1):17–30CrossRefGoogle Scholar
  11. 11.
    Itzkowitz SH, Jandorf L, Brand R et al (2007) Improved fecal DNA test for colorectal cancer screening. Clin Gastroenterol Hepatol 5:111–117CrossRefGoogle Scholar
  12. 12.
    Heichman KA, Warren JD (2012) DNA methylation biomarkers and their utility for solid cancer diagnostics. Clin Chem Lab Med 50:1707–1721CrossRefGoogle Scholar
  13. 13.
    Ellinger J, Haan K, Heukamp LC et al (2008) CpG Island hypermethylation in cell-free serum DNA identifies patients with localized prostate cancer. Prostate 68:42–49CrossRefGoogle Scholar
  14. 14.
    Sharma G, Mirza S, Parshad R et al (2010) Clinical significance of promoter hypermethylation of DNA repair genes in tumor and serum DNA in invasive ductal breast carcinoma patients. Life Sci 87:83–91CrossRefGoogle Scholar
  15. 15.
    Warton K, Samimi G (2015) Methylation of cell-free circulating DNA in the diagnosis of cancer. Front Mol Biosci 2:13. eCollection 2015CrossRefGoogle Scholar
  16. 16.
    Grutzmann R, Molnar B, Pilarsky C et al (2008) Sensitive detection of colorectal cancer in peripheral blood by septin 9 DNA methylation assay. PLoS One 3:e3759CrossRefGoogle Scholar
  17. 17.
    Devos T, Tetzner R, Model F et al (2009) Circulating methylated SEPT9 DNA in plasma is a biomarker for colorectal cancer. Clin Chem 55:1337–1346CrossRefGoogle Scholar
  18. 18.
    Warren JD, Xiong W, Bunker AM et al (2011) Septin 9 methylated DNA is a sensitive and specific blood test for colorectal cancer. BMC Med 9:133CrossRefGoogle Scholar
  19. 19.
    Church TR, Wandell M, Lofton-Day C et al (2014) Prospective evaluation of methylated SEPT9 in plasma for detection of asymptomatic colorectal cancer. Gut 63:317–325CrossRefGoogle Scholar
  20. 20.
    U.S. Food and Drug Administration. PMA Number P130001. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMA/pma.cfm?id=P130001. Accessed 27 Apr 2017
  21. 21.
    Cassinotti E, Melson J, Liggett T et al (2011) DNA methylation patterns in blood of patients with colorectal cancer and adenomatous colorectal polyps. Int J Cancer 131:1153–1157CrossRefGoogle Scholar
  22. 22.
    Pack SC, Kim HR, Lim SW et al (2013) Usefulness of plasma epigenetic changes of five major genes involved in the pathogenesis of colorectal cancer. Int J Color Dis 28:139–147CrossRefGoogle Scholar
  23. 23.
    Wu T, Giovannucci E, Welge J (2011) Measurement of GSTP1 promoter methylation in body fluids may complement PSA screening: a meta-analysis. Br J Cancer 105(1):65–73CrossRefGoogle Scholar
  24. 24.
    Dumache R, Puiu M, Motoc M (2014) Prostate cancer molecular detection in plasma samples by glutathione S-transferase P1 (GSTP1) methylation analysis. Clin Lab 60(5):847–852PubMedGoogle Scholar
  25. 25.
    Gurioli G, Salvi S, Martignano F et al (2016) Methylation pattern analysis in prostate cancer tissue: identification of biomarkers using an MS-MLPA approach. J Transl Med 14(1):249CrossRefGoogle Scholar
  26. 26.
    Martignano F, Gurioli G, Salvi S et al (2016) GSTP1 methylation and protein expression in prostate cancer: diagnostic implications. Dis Markers 2016:4358292CrossRefGoogle Scholar
  27. 27.
    Gurioli G, Martignano F, Salvi S et al (2018) GSTP1 methylation in cancer: a liquid biopsy biomarker? Clin Chem Lab Med 56(5):702–717CrossRefGoogle Scholar
  28. 28.
    Ellinger J, Bastian PJ, Jurgan T et al (2008) CpG island hypermethylation at multiple gene sites in diagnosis and prognosis of prostate cancer. Urology 71:161–167CrossRefGoogle Scholar
  29. 29.
    Chuang CK, Chu DC, Tzou RD, Liou SI et al (2007) Hypermethylation of the CpG islands in the promoter region flanking GSTP1 gene is a potential plasma DNA biomarker for detecting prostate carcinoma. Cancer Detect Prev 31:59–63CrossRefGoogle Scholar
  30. 30.
    Radpour R, Barekati Z, Kohler C et al (2011) Hypermethylation of tumor suppressor genes involved in critical regulatory pathways for developing a blood-based test in breast cancer. PLoS One 6:e16080CrossRefGoogle Scholar
  31. 31.
    Wang YC, Hsu HS, Chen TP, Chen JT (2006) Molecular diagnostic markers for lung cancer in sputum and plasma. Ann N Y Acad Sci 1075:179–184CrossRefGoogle Scholar
  32. 32.
    Hsu HS, Chen TP, Hung CH et al (2007) Characterization of a multiple epigenetic marker panel for lung cancer detection and risk assessment in plasma. Cancer 110:2019–2026CrossRefGoogle Scholar
  33. 33.
    Zhang Y, Wang R, Song H, Huang G, Yi J, Zheng Y et al (2011) Methylation of multiple genes as a candidate biomarker in non-small cell lung cancer. Cancer Lett 303:21–28CrossRefGoogle Scholar
  34. 34.
    Kneip C, Schmidt B, Seegebarth A et al (2011) SHOX2 DNA methylation is a biomarker for the diagnosis of lung cancer in plasma. J Thorac Oncol 6:1632–1638CrossRefGoogle Scholar
  35. 35.
    Powrozek T, Krawczyk P, Kucharczyk T, Milanowski J (2014) Septin 9 promoter region methylation in free circulating DNA-potential role in noninvasive diagnosis of lung cancer: preliminary report. Med Oncol 31:917CrossRefGoogle Scholar
  36. 36.
    Ostrow KL, Michailidi C, Guerrero-Preston R, Hoque MO, Greenberg A, Rom W et al (2013) Cigarette smoke induces methylation of the tumor suppressor gene NISCH. Epigenetics 8:383–388CrossRefGoogle Scholar
  37. 37.
    Melnikov AA, Scholtens D, Talamonti MS et al (2009) Methylation profile of circulating plasma DNA in patients with pancreatic cancer. JSurgOncol 99:119–122Google Scholar
  38. 38.
    Liggett TE, Melnikov A, Yi Q et al (2011) Distinctive DNA methylation patterns of cell-free plasma DNA in women with malignant ovarian tumors. GynecolOncol 120:113–120Google Scholar
  39. 39.
    Melnikov A, Scholtens D, Godwin A, Levenson V (2009) Differential methylation profile of ovarian cancer in tissues and plasma. J Mol Diagn 11:60–65CrossRefGoogle Scholar
  40. 40.
    Ibanez de Caceres I, Battagli C, Esteller M et al (2004) Tumor cell-specific BRCA1 and RASSF1A hypermethylation in serum, plasma, and peritoneal fluid from ovarian cancer patients. Cancer Res 64(18):6476–6481CrossRefGoogle Scholar
  41. 41.
    Bastian PJ, Palapattu GS, Lin X et al (2005) Preoperative serum DNA GSTP1 CpG island hypermethylation and the risk of early prostate-specific antigen recurrence following radical prostatectomy. Clin Cancer Res 11:4037–4043CrossRefGoogle Scholar
  42. 42.
    Sunami E, Shinozaki M, Higano CS et al (2009) Multimarker circulating DNA assay for assessing blood of prostate cancer patients. Clin Chem 55:559–567CrossRefGoogle Scholar
  43. 43.
    Brait M, Banerjee M, Maldonado L et al (2017) Promoter methylation of MCAM, ERalpha and ERbeta in serum of early stage prostate cancer patients. Oncotarget 8:15431–15440CrossRefGoogle Scholar
  44. 44.
    Chen J, Gong M, Lu S et al (2013) Detection of serum Alu element hypomethylation for the diagnosis and prognosis of glioma. J Mol Neurosci 50(2):368–375CrossRefGoogle Scholar
  45. 45.
    Fujita N, Nakayama T, Yamamoto N et al (2012) Methylated DNA and total DNA in serum detected by one-step methylation-specific PCR is predictive of poor prognosis for breast cancer patients. Oncology 83:273–282CrossRefGoogle Scholar
  46. 46.
    Takahashi H, Kagara N, Tanei T et al (2017) Correlation of methylated circulating tumor DNA with response to neoadjuvant chemotherapy in breast cancer patients. Clin Breast Cancer 17:61–69. e63CrossRefGoogle Scholar
  47. 47.
    Lui YY, Chik KW, Chiu RW et al (2002) Predominant hematopoietic origin of cell-free DNA in plasma and serum after sex-mismatched bone marrow transplantation. Clin Chem 48:421–427PubMedGoogle Scholar
  48. 48.
    Lofton-Day C, Model F, Devos T et al (2008) DNA methylation biomarkers for blood-based colorectal cancer screening. Clin Chem 54:414423CrossRefGoogle Scholar
  49. 49.
    Bryzgunova OE, Morozkin ES, Yarmoschuk SV et al (2008) Methylation-specific sequencing of GSTP1 gene promoter in circulating/extracellular DNA from blood and urine of healthy donors and prostate cancer patients. Ann N Y Acad Sci 1137:222–225CrossRefGoogle Scholar
  50. 50.
    Song BP, Jain S, Lin SY et al (2012) Detection of hypermethylated vimentin in urine of patients with colorectal cancer. J Mol Diagn 14:112–119CrossRefGoogle Scholar
  51. 51.
    Schulz WA, Steinhoff C, Florl AR (2006) Methylation of endogenous human retroelements in health and disease. Curr Top Microbiol Immunol 310:211–250PubMedGoogle Scholar
  52. 52.
    Ghanjati F, Beermann A, Hermanns T et al (2014) Unreserved application of epigenetic methods to define differences of DNA methylation between urinary cellular and cell-free DNA. Cancer Biomark 14(5):295–302CrossRefGoogle Scholar
  53. 53.
    Reddington JP, Pennings S, Meehan RR (2013) Non-canonical functions of the DNA methylome in gene regulation. Biochem J 451(1):13–23CrossRefGoogle Scholar
  54. 54.
    Payne SR, Serth J, Schostak M et al (2009) DNA methylation biomarkers of prostate cancer: confirmation of candidates and evidence urine is the most sensitive body fluid for non invasive detection. Prostate 69:1257–1269CrossRefGoogle Scholar
  55. 55.
    Hoque MO, Topaloglu O, Begum S et al (2005) Quantitative methylation-specific polymerase chain reaction gene patterns in urine sediment distinguish prostate cancer patients from control subjects. J Clin Oncol 23:6569–6575CrossRefGoogle Scholar
  56. 56.
    Baylin SB, Jones PA (2011) A decade of exploring the cancer epigenome—biological and translational implications. Nat Rev Cancer 11(10):726–734CrossRefGoogle Scholar
  57. 57.
    Plass C, Pfister SM, Lindroth AM et al (2013) Mutations in regulators of the epigenome and their connections to global chromatin patterns in cancer. Nat Rev Genet 14(11):765–780CrossRefGoogle Scholar
  58. 58.
    Turcan S, Rohle D, Goenka A et al (2012) IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype. Nature 483(7390):479–483CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Biosciences LaboratoryIstituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCSMeldolaItaly

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