Skip to main content
SpringerLink
Log in

Methylation Analysis in Cancer

(Epi)Genomic Fast Track from Discovery to Clinical Routine

  • Chapter
DNA Methylation and Cancer Therapy

Part of the book series: Medical Intelligence Unit ((MIUN))

  • 1092 Accesses

Abstract

Aberrant DNA methylation is an early and common event in human cancers. Methylation acts as an epigenetic regulator of gene expression and is involved in cancer development as well as resistance to drug treatments. Specific methylation patterns have been shown for different cancer types and there is evidence that methylation can be used as a diagnostic tool. Several methods have been developed to study methylation on a genome wide basis. However they are labor intensive and can assess only a limited number of tissues at a time preventing the assessment of these genes in larger populations. Methylation microarrays now offer the possibility to validate these candidate genes statistically filling the gap between genome wide discovery methods and single gene assays which could be adjusted to routine clinical use. Here we show how all these methods can be combined to broaden our knowledge regarding DNA methylation and transform some of this information into powerful diagnostic tests.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bird A. The essentials of DNA methylation. Cell 1992; 70:5–8.

    Article  PubMed  CAS  Google Scholar 

  2. Cooper DN, Krawczak M. Cytosine methylation and the fate of CpG dinucleotides in vertebrate genomes. Hum Genet 1989; 83:181–188.

    Article  PubMed  CAS  Google Scholar 

  3. Larsen F, Gundersen G, Lopez R et al. CpG islands as gene markers in the human genome. Genomics 1992; 13:1095–1107.

    Article  PubMed  CAS  Google Scholar 

  4. Taylor SM, Jones PA. Multiple new phenotypes induced in 10T1/2 and 3T3 cells treated with 5-azacytidine. Cell 1979; 17:771–779.

    Article  PubMed  CAS  Google Scholar 

  5. Yievin A, Razin A. Gene methylation patterns and expression. In: Jost JP, Saluz HP, eds. DNA methylation: Molecular and Biological Significance. Basel: Birkhauser Verlag, 1993:523–568.

    Google Scholar 

  6. Nguyen CT, Gonzales FA, Jones PA et al. Altered chromatin structure associated with methylation-induced gene silencing in cancer cells: correlation of accessibility, methylation, MeCP2 binding and acetylation. Nuc Acids Res 2001; 29(22):4598–4606.

    Article  CAS  Google Scholar 

  7. Jones P, Veentra GJ, Wade PA et al. Methylated DNA and MePC2 recruit histone deacetylase to repress transcription. Nature Genet 1998:19:187–191.

    Article  PubMed  CAS  Google Scholar 

  8. Jones PA. DNA methylation errors and cancer. Cancer Res 1996; 56:2463–2467.

    PubMed  CAS  Google Scholar 

  9. Feinberg AP, Vogelstein B. Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature 1983; 301:89–92.

    Article  PubMed  CAS  Google Scholar 

  10. Jones PA, Laird PW. Cancer epigenetics comes of age. Nature Genet 1999; 21:163–167.

    Article  PubMed  CAS  Google Scholar 

  11. Cooper DN, Youssoufian H. The CpG dinucleotide and human genetic disease. Hum Genet 1988;78:151–155.

    Article  PubMed  CAS  Google Scholar 

  12. Jiricny J. Mismatch repair and cancer. Cancer Surveys: Genetic instability in Cancer. Imperial Cancer Research Fund 1996; 28:47–68.

    CAS  Google Scholar 

  13. Shen JC, Rideout WM, Jones PA. The rate of hydrolitic deamination of 5-methylcytosine in double stranded DNA. Nucleic Acids Res 1994; 22:972–976.

    Article  PubMed  CAS  Google Scholar 

  14. Lieb M, Rehmat S. 5-methylcytosine is not a mutagen hot spot in non dividing Escherichia Coli. Proc Natl Acad Sci USA 1997; 94:940–945.

    Article  PubMed  CAS  Google Scholar 

  15. Shen JC, Rideout WM, Jones PA. High frequency mutagenesis by a DNA methyltransferase. Cell 1992; 71:1073–1080.

    Article  PubMed  CAS  Google Scholar 

  16. Soria J-C, Rodriguez M, Liu DD et al. Aberrant promoter methylation of multiple genes in bronchial brush samples form former cigarette smokers. Cancer Res 2002; 62:351–355.

    PubMed  CAS  Google Scholar 

  17. Tommasi S, Denissenko MF, Pfeifer GP. Sunlight induces pyrimdine dimers preferentially at 5-methylcytosine bases. Cancer Res 1997; 57:4727–4730.

    PubMed  CAS  Google Scholar 

  18. Rhee I, Bachman KE, Park BH et al. DNMT1 and DNMT3b cooperate to silence genes in human cancer cells. Nature 2002; 416:552–556.

    Article  PubMed  CAS  Google Scholar 

  19. Nguyen C, Liang G, Nguyen TT et al. Susceptibility of non promoter CpG islands to de novo methylation in normal and neoplastic cells. J Nat Cancer Inst 2001; 93(19):1465–1472.

    Article  PubMed  CAS  Google Scholar 

  20. Esteller M, corn PG, Baylin SB et al. A gene hypermethylation profile of human cancer. Cancer Res 2001; 61:3225–3229.

    PubMed  CAS  Google Scholar 

  21. Toyota M, Ahuja N, Ohe-Toyota M et al. CpG island methylator phenotype in colorectal cancer. Proc Natl Acad Sci USA 1999; 96:8681–8686.

    Article  PubMed  CAS  Google Scholar 

  22. Deng G, Peng E, Gum J et al. Methylation of hMLH1 promoter correlates with silencing with a region-specific manner in colorectal cancer. Br J Cancer 2002; 86(4):574–579.

    Article  PubMed  CAS  Google Scholar 

  23. Yi J, Wang ZW, Cang H et al. P16 gene methylation in colorectal cancers associated with Duke’s staging. World J Gastroenterol 2001; 7(5):722–725.

    PubMed  CAS  Google Scholar 

  24. Zou HZ, Yu BM, Wang ZW et al. Clin Cancer Res 2002; 8(1):188–191.

    PubMed  Google Scholar 

  25. Yamamoto H Min Y, Itoh F, Imsumran A et al. Differential involvement of the hypermethylator phenotype in hereditary and sporadic colorectal cancers with high frequency microsatellite instability. Genes Chromosomes Cancer 2002; 33(3):322–325.

    Article  PubMed  CAS  Google Scholar 

  26. Rashid A, Shen L, Morris JS et al. CpG island methylation in colorectal adenomas. Am J Pathol 2001; 159(3):1129–1135.

    PubMed  CAS  Google Scholar 

  27. Isaacs WB, Isaacs JT. Molecular genetics of prostate cancer progression. In: Ravanagh D, Liebel SA, Schar HI, Lange P, eds. Principles and practice of genotourinary oncology. Philadelphia, New York: Lippincott-Raven Publishers, 1996:403–408.

    Google Scholar 

  28. Cairns P, Okami K, Halachmi S et al. Frequent inactivation of PTEN/MMAC1 in primary prostate cancer. Cancer Res 1997; 57:4997–5000.

    PubMed  CAS  Google Scholar 

  29. Lee WH, Isaacs WB, Bova GS et al. CG island methylation changes near the GSTP1 gene in prostatic carcinoma cells detected using the polymerase chain reaction: a new prostate biomarker. Cancer Epidemiol Biomark Prev 1997; 6:443–450.

    CAS  Google Scholar 

  30. Millar DS, Ow KK, Paul CL et al. Detailed methylation analysis of the glutathione S-transferase π (GSTP1) gene in prostate cancer. Oncogene 1999; 18:1313–1324.

    Article  PubMed  CAS  Google Scholar 

  31. Mannrvik B, Alin P, Guthenberg G et al. Identification of three classes of cytosolic glutathione transferase common to several mammalian species: correlation between structural data and enzymatic properties. Proc Natl Acad Sci USA 1985; 82:7202–7206.

    Article  Google Scholar 

  32. Lee WH, Morton RA, Epstein JI et al. Cytidine methylation of regulatory sequences near the π-class glutathione S-transferase gene accompanies human prostatic carcinogenesis. Proct Natl Acad Sci USA 1994; 91:11733–11737.

    Article  CAS  Google Scholar 

  33. Brooks JD, Weinstein M, Lin X et al. CG island methylation changes near the GSTP1 gene in prostatic intraepithelial neoplasia. Cancer Epidemiol Biomark Prev 1998; 7:531–536.

    CAS  Google Scholar 

  34. Goessl C, Krause H, Müller M et al. Fluorescent Methylation-Specific Polymerase Chain Reaction for DNA-based detection of prostate cancer in bodily fluids. Cancer Res 2000; 60:5941–5945.

    PubMed  CAS  Google Scholar 

  35. Goessl C, Müller M, Heicappell R et al. Methylation-specific PCR for detection of neoplastic DNA in biopsy washing. J Pathol 2002; 196(3):331–334.

    Article  PubMed  CAS  Google Scholar 

  36. Chu DC, Chuang CK, Fu JB et al. The use of real time quantitative polymerase chain reaction to detect hypermethylation of the CpG islands in the promoter region flanking the GSTPl gene to diagnose prostate cancer. J Urol 2002; 167(4):1854–1858.

    Article  PubMed  CAS  Google Scholar 

  37. Hatada I, Hayashizaka Y, Hirotsune S et al. A genomic scanning method for higher organisms using restriction sites as landmarks. Proc Natl Acad Sci USA 1991; 88:9523–9527.

    Article  PubMed  CAS  Google Scholar 

  38. Hayashizaki Y, Shibata H, Hirotsune S et al. Identification of an imprinted U2af binding protein related sequence on mouse chromosome 11 using the RLGS method. Nat Genet 1994; 6:33–40.

    Article  PubMed  CAS  Google Scholar 

  39. Costello JF, Frühwald MC, Smiraglia DJ et al. Aberrant Cpl-island methylation has nonrandom and tumor-type specific patterns. Nat Genet 2000; 25:132–138.

    Article  Google Scholar 

  40. Kuick T, Asakawa J, Neel J et al. High yield of restriction fragment length polymorphisms in two-dimensional separation of human genomic DNA. Genomics 1995; 13:1095–1107.

    Google Scholar 

  41. Huang THM, Perry M, Laux D. Methylation profiling of CpG islands in human breast cancer cells. Hum Mol Genet 1999; 8(3):459–470.

    Article  PubMed  CAS  Google Scholar 

  42. Gonzalgo ML, Liang G, Spruck III CH et al. Identification and characterization of differentially methylated regions of genomic DNA by methylation-sensitive arbitrarily primed PCR. Cancer Res 1999; 57:594–599.

    Google Scholar 

  43. Toyota M, Coty H, Ahuja N et al. Identification of differentially methylated sequences in colorectal cancer by methylated Cpl island amplification. Cancer Res 1999; 59:2307–2312.

    PubMed  CAS  Google Scholar 

  44. Adorjan P, Distler J, Lipscher E et al. Tumour class prediction and discovery by microarray-based DNA methylation analysis. Nuc Acids Res 2002; 30(5)e21.

    Article  Google Scholar 

  45. Frommer M, Mc Donald LE, Millar DS et al. A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands. Proc Natl Acad Sci USA 1992; 89:1827–1831.

    Article  PubMed  CAS  Google Scholar 

  46. Mendenhall W, Sincich T. Statistics for Engeneering and the Sciences NJ: Prentice Hall, 1995.

    Google Scholar 

  47. Lipshutz RJ, Fodor S PA, Gingeras TR et al. High density synthetic oligonucleotide arrays. Nature Genet 1999; 21(suppl):25–32.

    Google Scholar 

  48. Palmisano W, Divine KK, Saccomanno G et al. Predicting Lung Cancer by detecting aberrant promoter methylation in sputum. Cancer Res 2000; 60:5954–5958.

    PubMed  CAS  Google Scholar 

  49. Eads CA, Danenberg KD, Kawakami K et al. Methylight: a high-throughput assay to measure DNA methylation. Nuc Acid Res 2000; 28(8):e32.

    Article  CAS  Google Scholar 

  50. Cotrell SE, Distler J, Goodman NS et al. unpublished data.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Epigenomics AG, Berlin, Germany

    Carolina Haefliger, Sabine Maier & Alexander Olek

Authors
  1. Carolina Haefliger
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sabine Maier
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alexander Olek
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Eurekah.com and Kluwer Academic/Plenum Publishers

About this chapter

Cite this chapter

Haefliger, C., Maier, S., Olek, A. (2005). Methylation Analysis in Cancer. In: DNA Methylation and Cancer Therapy. Medical Intelligence Unit. Springer, Boston, MA. https://doi.org/10.1007/0-387-27443-X_9

Download citation

Publish with us

Policies and ethics

Search

Navigation