Advanced search
Publication Cover
Expert Review of Molecular Diagnostics Volume 13, 2013 - Issue 3
Submit an article Journal homepage
361
Views
16
CrossRef citations to date
0
Altmetric
Review

Challenges for the application of DNA methylation biomarkers in molecular diagnostic testing for cancer

Surbhi Jain Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 18901, USA; Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 18901, USA
,
Tomasz K Wojdacz Institute of Environmental Medicine, Karolinska Institutet, Nobels väg 13, Box 210, SE-17177 Stockholm, Sweden; Institute of Environmental Medicine, Karolinska Institutet, Nobels väg 13, Box 210, SE-17177 Stockholm, Sweden
&
Ying-Hsiu Su Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 18901, USA. [email protected]; Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 18901, USA. [email protected]
Pages 283-294 | Published online: 09 Jan 2014

References

  • Esteller M, Corn PG, Baylin SB, Herman JG. A gene hypermethylation profile of human cancer. Cancer Res. 61(8), 3225–3229 (2001).
  • Wood LD, Parsons DW, Jones S et al. The genomic landscapes of human breast and colorectal cancers. Science 318(5853), 1108–1113 (2007).
  • Jones PA, Baylin SB. The fundamental role of epigenetic events in cancer. Nat. Rev. Genet. 3(6), 415–428 (2002).
  • Shen J, Wang S, Zhang YJ et al. Genome-wide DNA methylation profiles in hepatocellular carcinoma. Hepatology 55(6), 1799–1808 (2012).
  • Guichard C, Amaddeo G, Imbeaud S et al. Integrated analysis of somatic mutations and focal copy-number changes identifies key genes and pathways in hepatocellular carcinoma. Nat. Genet. 44(6), 694–698 (2012).
  • Mikeska T, Bock C, Do H, Dobrovic A. DNA methylation biomarkers in cancer: progress towards clinical implementation. Expert Rev. Mol. Diagn. 12(5), 473–487 (2012).
  • Straussman R, Nejman D, Roberts D et al. Developmental programming of CpG island methylation profiles in the human genome. Nat. Struct. Mol. Biol. 16(5), 564–571 (2009).
  • Rainier S, Johnson LA, Dobry CJ, Ping AJ, Grundy PE, Feinberg AP. Relaxation of imprinted genes in human cancer. Nature 362(6422), 747–749 (1993).
  • Ogawa O, Eccles MR, Szeto J et al. Relaxation of insulin-like growth factor II gene imprinting implicated in Wilms’ tumour. Nature 362(6422), 749–751 (1993).
  • Wilson AS, Power BE, Molloy PL. DNA hypomethylation and human diseases. Biochim. Biophys. Acta 1775(1), 138–162 (2007).
  • Baylin SB. DNA methylation and gene silencing in cancer. Nat. Clin. Pract. Oncol. 2(Suppl. 1), S4–S11 (2005).
  • Homma N, Tamura G, Honda T et al. Spreading of methylation within RUNX3 CpG island in gastric cancer. Cancer Sci. 97(1), 51–56 (2006).
  • Buffart TE, Overmeer RM, Steenbergen RD et al. MAL promoter hypermethylation as a novel prognostic marker in gastric cancer. Br. J. Cancer 99(11), 1802–1807 (2008).
  • Gigek CO, Leal MF, Silva PN et al. hTERT methylation and expression in gastric cancer. Biomarkers 14(8), 630–636 (2009).
  • Deng G, Chen A, Hong J, Chae HS, Kim YS. Methylation of CpG in a small region of the hMLH1 promoter invariably correlates with the absence of gene expression. Cancer Res. 59(9), 2029–2033 (1999).
  • Yoshikawa H, Matsubara K, Qian GS et al. SOCS-1, a negative regulator of the JAK/STAT pathway, is silenced by methylation in human hepatocellular carcinoma and shows growth-suppression activity. Nat. Genet. 28(1), 29–35 (2001).
  • Jain S, Yoon SY, Zhu L et al. Arf4 determines dentate gyrus-mediated pattern separation by regulating dendritic spine development. PLoS ONE 7(9), e46340 (2012).
  • Jain S, Chang TT, Hamilton JP et al. Methylation of the CpG sites only on the sense strand of the APC gene is specific for hepatocellular carcinoma. PLoS ONE 6(11), e26799 (2011).
  • van Vlodrop IJ, Niessen HE, Derks S et al. Analysis of promoter CpG island hypermethylation in cancer: location, location, location! Clin. Cancer Res. 17(13), 4225–4231 (2011).
  • Millar DS, Paul CL, Molloy PL, Clark SJ. A distinct sequence (ATAAA)n separates methylated and unmethylated domains at the 5´-end of the GSTP1 CpG island. J. Biol. Chem. 275(32), 24893–24899 (2000).
  • Di Gioia S, Bianchi P, Destro A et al. Quantitative evaluation of RASSF1A methylation in the non-lesional, regenerative and neoplastic liver. BMC Cancer 6, 89 (2006).
  • Yeo W, Wong N, Wong WL, Lai PB, Zhong S, Johnson PJ. High frequency of promoter hypermethylation of RASSF1A in tumor and plasma of patients with hepatocellular carcinoma. Liver Int. 25(2), 266–272 (2005).
  • Um TH, Kim H, Oh BK et al. Aberrant CpG island hypermethylation in dysplastic nodules and early HCC of hepatitis B virus-related human multistep hepatocarcinogenesis. J. Hepatol. 54(5), 939–947 (2011).
  • Yan PS, Shi H, Rahmatpanah F et al. Differential distribution of DNA methylation within the RASSF1A CpG island in breast cancer. Cancer Res. 63(19), 6178–6186 (2003).
  • Suzuki MM, Bird A. DNA methylation landscapes: provocative insights from epigenomics. Nat. Rev. Genet. 9(6), 465–476 (2008).
  • Bird A. DNA methylation patterns and epigenetic memory. Genes Dev. 16(1), 6–21 (2002).
  • Illingworth R, Kerr A, Desousa D et al. A novel CpG island set identifies tissue-specific methylation at developmental gene loci. PLoS Biol. 6(1), e22 (2008).
  • Eckhardt F, Lewin J, Cortese R et al. DNA methylation profiling of human chromosomes 6, 20 and 22. Nat. Genet. 38(12), 1378–1385 (2006).
  • Song F, Mahmood S, Ghosh S et al. Tissue specific differentially methylated regions (TDMR): changes in DNA methylation during development. Genomics 93(2), 130–139 (2009).
  • Portela A, Esteller M. Epigenetic modifications and human disease. Nat. Biotechnol. 28(10), 1057–1068 (2010).
  • Hosoya K, Yamashita S, Ando T, Nakajima T, Itoh F, Ushijima T. Adenomatous polyposis coli 1A is likely to be methylated as a passenger in human gastric carcinogenesis. Cancer Lett. 285(2), 182–189 (2009).
  • Dobrovic A, Kristensen LS. DNA methylation, epimutations and cancer predisposition. Int. J. Biochem. Cell Biol. 41(1), 34–39 (2009).
  • Wojdacz TK, Thestrup BB, Cold S, Overgaard J, Hansen LL. No difference in the frequency of locus-specific methylation in the peripheral blood DNA of women diagnosed with breast cancer and age-matched controls. Future Oncol. 7(12), 1451–1455 (2011).
  • Snell C, Krypuy M, Wong EM, Loughrey MB, Dobrovic A; kConFab investigators. BRCA1 promoter methylation in peripheral blood DNA of mutation negative familial breast cancer patients with a BRCA1 tumour phenotype. Breast Cancer Res. 10(1), R12 (2008).
  • Chai H, Brown RE. Field effect in cancer – an update. Ann. Clin. Lab. Sci. 39(4), 331–337 (2009).
  • Nishida N, Nagasaka T, Nishimura T, Ikai I, Boland CR, Goel A. Aberrant methylation of multiple tumor suppressor genes in aging liver, chronic hepatitis, and hepatocellular carcinoma. Hepatology 47(3), 908–918 (2008).
  • Sherman M. Recurrence of hepatocellular carcinoma. N. Engl. J. Med. 359(19), 2045–2047 (2008).
  • Yang JD, Nakamura I, Roberts LR. The tumor microenvironment in hepatocellular carcinoma: current status and therapeutic targets. Semin. Cancer Biol. 21(1), 35–43 (2011).
  • Giovannucci E, Ogino S. DNA methylation, field effects, and colorectal cancer. J. Natl Cancer Inst. 97(18), 1317–1319 (2005).
  • Hoshida Y, Villanueva A, Llovet JM. Molecular profiling to predict hepatocellular carcinoma outcome. Expert Rev. Gastroenterol. Hepatol. 3(2), 101–103 (2009).
  • Toyota M, Ahuja N, Suzuki H et al. Aberrant methylation in gastric cancer associated with the CpG island methylator phenotype. Cancer Res. 59(21), 5438–5442 (1999).
  • Viet CT, Schmidt BL. Methylation array analysis of preoperative and postoperative saliva DNA in oral cancer patients. Cancer Epidemiol. Biomarkers Prev. 17(12), 3603–3611 (2008).
  • Reinert T, Modin C, Castano FM et al. Comprehensive genome methylation analysis in bladder cancer: identification and validation of novel methylated genes and application of these as urinary tumor markers. Clin. Cancer Res. 17(17), 5582–5592 (2011).
  • Cairns P, Esteller M, Herman JG et al. Molecular detection of prostate cancer in urine by GSTP1 hypermethylation. Clin. Cancer Res. 7(9), 2727–2730 (2001).
  • Cairns P. Detection of promoter hypermethylation of tumor suppressor genes in urine from kidney cancer patients. Ann. NY Acad. Sci. 1022, 40–43 (2004).
  • de Fraipont F, Moro-Sibilot D, Michelland S, Brambilla E, Brambilla C, Favrot MC. Promoter methylation of genes in bronchial lavages: a marker for early diagnosis of primary and relapsing non-small cell lung cancer? Lung Cancer 50(2), 199–209 (2005).
  • Lee A, Kim Y, Han K, Kang CS, Jeon HM, Shim SI. Detection of tumor markers including carcinoembryonic antigen, APC, and cyclin D2 in fine-needle aspiration fluid of breast. Arch. Pathol. Lab. Med. 128(11), 1251–1256 (2004).
  • Lind GE, Danielsen SA, Ahlquist T et al. Identification of an epigenetic biomarker panel with high sensitivity and specificity for colorectal cancer and adenomas. Mol. Cancer 10, 85 (2011).
  • Jung K, Fleischhacker M, Rabien A. Cell-free DNA in the blood as a solid tumor biomarker – a critical appraisal of the literature. Clin. Chim. Acta 411(21–22), 1611–1624 (2010).
  • Schwarzenbach H, Chun FK, Isbarn H, Huland H, Pantel K. Genomic profiling of cell-free DNA in blood and bone marrow of prostate cancer patients. J. Cancer Res. Clin. Oncol. 137(5), 811–819 (2011).
  • Chan KC, Lai PB, Mok TS et al. Quantitative analysis of circulating methylated DNA as a biomarker for hepatocellular carcinoma. Clin. Chem. 54(9), 1528–1536 (2008).
  • Wong IH, Zhang J, Lai PB, Lau WY, Lo YM. Quantitative analysis of tumor-derived methylated p16INK4a sequences in plasma, serum, and blood cells of hepatocellular carcinoma patients. Clin. Cancer Res. 9(3), 1047–1052 (2003).
  • Tsutsui M, Iizuka N, Moribe T et al. Methylated cyclin D2 gene circulating in the blood as a prognosis predictor of hepatocellular carcinoma. Clin. Chim. Acta 411(7–8), 516–520 (2010).
  • Kirk GD, Lesi OA, Mendy M et al. 249(ser) TP53 mutation in plasma DNA, hepatitis B viral infection, and risk of hepatocellular carcinoma. Oncogene 24(38), 5858–5867 (2005).
  • Warren JD, Xiong W, Bunker AM et al. Septin 9 methylated DNA is a sensitive and specific blood test for colorectal cancer. BMC Med. 9, 133 (2011).
  • Su YH, Wang M, Aiamkitsumrit B, Brenner DE, Block TM. Detection of a K-ras mutation in urine of patients with colorectal cancer. Cancer Biomark. 1(2–3), 177–182 (2005).
  • Su YH, Song J, Wang Z et al. Removal of high-molecular-weight DNA by carboxylated magnetic beads enhances the detection of mutated K-ras DNA in urine. Ann. NY Acad. Sci. 1137, 82–91 (2008).
  • Su YH, Wang M, Brenner DE et al. Human urine contains small, 150 to 250 nucleotide-sized, soluble DNA derived from the circulation and may be useful in the detection of colorectal cancer. J. Mol. Diagn. 6(2), 101–107 (2004).
  • Su YH, Wang M, Brenner DE, Norton PA, Block TM. Detection of mutated K-ras DNA in urine, plasma, and serum of patients with colorectal carcinoma or adenomatous polyps. Ann. NY Acad. Sci. 1137, 197–206 (2008).
  • Melkonyan HS, Feaver WJ, Meyer E et al. Transrenal nucleic acids: from proof of principle to clinical tests. Ann. NY Acad. Sci. 1137, 73–81 (2008).
  • Chan AK, Chiu RW, Lo YM; Clinical Sciences Reviews Committee of the Association of Clinical Biochemists. Cell-free nucleic acids in plasma, serum and urine: a new tool in molecular diagnosis. Ann. Clin. Biochem. 40(Pt 2), 122–130 (2003).
  • Serdyuk OI, Botezatu IV, Shelepov VP et al. Detection of mutant k-ras sequences in the urine of cancer patients. Bull. Exp. Biol. Med. 131(3), 283–284 (2001).
  • Botezatu I, Serdyuk O, Potapova G et al. Genetic analysis of DNA excreted in urine: a new approach for detecting specific genomic DNA sequences from cells dying in an organism. Clin. Chem. 46(8 Pt 1), 1078–1084 (2000).
  • Lichtenstein AV, Melkonyan HS, Tomei LD, Umansky SR. Circulating nucleic acids and apoptosis. Ann. NY Acad. Sci. 945, 239–249 (2001).
  • Jahr S, Hentze H, Englisch S et al. DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells. Cancer Res. 61(4), 1659–1665 (2001).
  • Lin SY, Dhillon V, Jain S et al. A locked nucleic acid clamp-mediated PCR assay for detection of a p53 codon 249 hotspot mutation in urine. J. Mol. Diagn. 13(5), 474–484 (2011).
  • Song BP, Jain S, Lin SY et al. Detection of hypermethylated vimentin in urine of patients with colorectal cancer. J. Mol. Diagn. 14(2), 112–119 (2012).
  • Lin SL, Jain S, Song W, Hu C-T, Su Y-H. Strategic assay developments for detection of HBV 1762T/1764A double mutation in urine of patients with HBV-associated hepatocellular carcinomas. Lau W-Y (Ed.). In: Hepatocellular Carcinoma – Clinical Research. InTech, Rijeka, Croatia, 139–154 (2012).
  • Diehl F, Schmidt K, Durkee KH et al. Analysis of mutations in DNA isolated from plasma and stool of colorectal cancer patients. Gastroenterology 135(2), 489–498 (2008).
  • Chan KC, Leung SF, Yeung SW, Chan AT, Lo YM. Quantitative analysis of the transrenal excretion of circulating EBV DNA in nasopharyngeal carcinoma patients. Clin. Cancer Res. 14(15), 4809–4813 (2008).
  • Shekhtman EM, Anne K, Melkonyan HS, Robbins DJ, Warsof SL, Umansky SR. Optimization of transrenal DNA analysis: detection of fetal DNA in maternal urine. Clin. Chem. 55(4), 723–729 (2009).
  • Sikora A, Zimmermann BG, Rusterholz C et al. Detection of increased amounts of cell-free fetal DNA with short PCR amplicons. Clin. Chem. 56(1), 136–138 (2010).
  • Mao R, Chou LS. Methylation analysis by restriction endonuclease digestion and real-time PCR. Clin. Chem. 56(7), 1050–1052 (2010).
  • Herman JG, Graff JR, Myöhänen S, Nelkin BD, Baylin SB. Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc. Natl Acad. Sci. USA 93(18), 9821–9826 (1996).
  • Aggerholm A, Hokland P. DAP-kinase CpG island methylation in acute myeloid leukemia: methodology versus biology? Blood 95(9), 2997–2999 (2000).
  • Rand K, Qu W, Ho T, Clark SJ, Molloy P. Conversion-specific detection of DNA methylation using real-time polymerase chain reaction (ConLight-MSP) to avoid false positives. Methods 27(2), 114–120 (2002).
  • Dobrovic A. Methods for analyses of DNA methylation. In: Molecular Diagnostics for the Clinical Laboratorian. Coleman WB, Tsongalis GJ (Eds). Humana Press, NJ, USA, (2005).
  • Wojdacz TK. Methylation-sensitive high-resolution melting in the context of legislative requirements for validation of analytical procedures for diagnostic applications. Expert Rev. Mol. Diagn. 12(1), 39–47 (2012).
  • Warnecke PM, Stirzaker C, Melki JR, Millar DS, Paul CL, Clark SJ. Detection and measurement of PCR bias in quantitative methylation analysis of bisulphite-treated DNA. Nucleic Acids Res. 25(21), 4422–4426 (1997).
  • Wojdacz TK, Hansen LL. Reversal of PCR bias for improved sensitivity of the DNA methylation melting curve assay. BioTechniques 41(3), 274, 276, 278 (2006).
  • Wojdacz TK, Hansen LL, Dobrovic A. A new approach to primer design for the control of PCR bias in methylation studies. BMC Res. Notes 1, 54 (2008).
  • Wojdacz TK, Borgbo T, Hansen LL. Primer design versus PCR bias in methylation independent PCR amplifications. Epigenetics 4(4), 231–234 (2009).
  • Eads CA, Danenberg KD, Kawakami K et al. MethyLight: a high-throughput assay to measure DNA methylation. Nucleic Acids Res. 28(8), E32 (2000).
  • Wojdacz TK, Møller TH, Thestrup BB, Kristensen LS, Hansen LL. Limitations and advantages of MS-HRM and bisulfite sequencing for single locus methylation studies. Expert Rev. Mol. Diagn. 10(5), 575–580 (2010).
  • Candiloro IL, Mikeska T, Dobrovic A. Assessing combined methylation-sensitive high resolution melting and pyrosequencing for the analysis of heterogeneous DNA methylation. Epigenetics 6(4), 500–507 (2011).
  • Wojdacz TK. The limitations of locus specific methylation qualification and quantification in clinical material. Front. Genet. 3, 21 (2012).
  • McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM; Statistics Subcommittee of the NCI-EORTC Working Group on Cancer Diagnostics. Reporting Recommendations for Tumour Marker Prognostic Studies (REMARK). Eur. J. Cancer 41(12), 1690–1696 (2005).
  • Fan HC, Gu W, Wang J, Blumenfeld YJ, El-Sayed YY, Quake SR. Non-invasive prenatal measurement of the fetal genome. Nature 487(7407), 320–324 (2012).

Websites

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.