Cell-free nucleic acids as biomarkers in cancer patients
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Mandel, P. & Métais, P. Les acides nucléiques du plasma sanguin chez l'homme. C. R. Acad. Sci. Paris 142, 241–243 (1948).
Sorenson, G. D. et al. Soluble normal and mutated DNA sequences from single-copy genes in human blood. Cancer Epidemiol. Biomarkers Prev. 3, 67–71 (1994).
Vasioukhin, V. et al. Point mutations of the N-ras gene in the blood plasma DNA of patients with myelodysplastic syndrome or acute myelogenous leukaemia. Br. J. Haematol. 86, 774–779 (1994).
Nawroz, H., Koch, W., Anker, P., Stroun, M. & Sidransky, D. Microsatellite alterations in serum DNA of head and neck cancer patients. Nature Med. 2, 1035–1037 (1996).
Swaminathan, R. & Butt, A. N. Circulating nucleic acids in plasma and serum: recent developments. Ann. N. Y Acad. Sci. 1075, 1–9 (2006). This review discusses the origin and biological importance of circulating nucleic acids in fetal medicine, oncology and other human-related diseases.
Fleischhacker, M. & Schmidt, B. Circulating nucleic acids (CNAs) and cancer-a survey. Biochim. Biophys. Acta 1775, 181–232 (2007).
Choi, J. J., Reich, C. F. 3rd, & Pisetsky, D. S. The role of macrophages in the in vitro generation of extracellular DNA from apoptotic and necrotic cells. Immunology 115, 55–62 (2005).
Stroun, M. et al. The origin and mechanism of circulating DNA. Ann. N. Y Acad. Sci. 906, 161–168 (2000).
Gahan, P. B. & Swaminathan, R. Circulating nucleic acids in plasma and serum. Recent developments. Ann. N. Y Acad. Sci. 1137, 1–6 (2008).
Diehl, F. et al. Detection and quantification of mutations in the plasma of patients with colorectal tumors. Proc. Natl Acad. Sci. USA 102, 16368–16373 (2005).
Jahr, 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, 1659–1665 (2001).
Schwarzenbach, H. et al. Cell-free tumor DNA in blood plasma as a marker for circulating tumor cells in prostate cancer. Clin. Cancer Res. 15, 1032–1038 (2009). A relationship between the occurrence of CTCs and circulating tumour-associated DNA in blood is described for the first time in patients with prostate cancer.
Schwarzenbach, H. et al. Detection of tumor-specific DNA in blood and bone marrow plasma from patients with prostate cancer. Int. J. Cancer 120, 1465–1471 (2007).
Bendich, A., Wilczok, T. & Borenfreund, E. Circulating DNA as a possible factor in oncogenesis. Science 148, 374–376 (1965).
Emlen, W. & Mannik, M. Effect of DNA size and strandedness on the in vivo clearance and organ localization of DNA. Clin. Exp. Immunol. 56, 185–192 (1984).
Wimberger, P. et al. Impact of platinum-based chemotherapy on circulating nucleic acid levels, protease activities in blood and disseminated tumor cells in bone marrow of ovarian cancer patients. Int. J. Cancer 128, 2572–2580 (2010). This is the first study indicating the potential value of circulating nucleosomes in monitoring the effects of chemotherapy in ovarian cancer.
Boddy, J. L., Gal, S., Malone, P. R., Harris, A. L. & Wainscoat, J. S. Prospective study of quantitation of plasma DNA levels in the diagnosis of malignant versus benign prostate disease. Clin. Cancer Res. 11, 1394–1399 (2005).
Kamat, A. A. et al. Plasma cell-free DNA in ovarian cancer: an independent prognostic biomarker. Cancer 116, 1918–1925 (2010).
Allen, D. et al. Role of cell-free plasma DNA as a diagnostic marker for prostate cancer. Ann. N. Y Acad. Sci. 1022, 76–80 (2004).
Schwarzenbach, H., Stoehlmacher, J., Pantel, K. & Goekkurt, E. Detection and monitoring of cell-free DNA in blood of patients with colorectal cancer. Ann. N. Y Acad. Sci. 1137, 190–196 (2008).
Chun, F. K. et al. Circulating tumour-associated plasma DNA represents an independent and informative predictor of prostate cancer. BJU Int. 98, 544–548 (2006).
Sunami, E., Vu, A. T., Nguyen, S. L., Giuliano, A. E. & Hoon, D. S. Quantification of LINE1 in circulating DNA as a molecular biomarker of breast cancer. Ann. N. Y Acad. Sci. 1137, 171–174 (2008).
Gormally, E. et al. Amount of DNA in plasma and cancer risk: a prospective study. Int. J. Cancer 111, 746–749 (2004).
Catarino, R. et al. Quantification of free circulating tumor DNA as a diagnostic marker for breast cancer. DNA Cell Biol. 27, 415–421 (2008).
Mehra, N. et al. Circulating mitochondrial nucleic acids have prognostic value for survival in patients with advanced prostate cancer. Clin. Cancer Res. 13, 421–426 (2007).
Ellinger, J., Albers, P., Muller, S. C., von Ruecker, A. & Bastian, P. J. Circulating mitochondrial DNA in the serum of patients with testicular germ cell cancer as a novel noninvasive diagnostic biomarker. BJU Int. 104, 48–52 (2009).
Chiu, R. W. et al. Quantitative analysis of circulating mitochondrial DNA in plasma. Clin. Chem. 49, 719–726 (2003). This is one of the first studies describing the technical approach and detection of mitochondria circulating DNA in plasma.
Tangkijvanich, P. et al. Serum LINE-1 hypomethylation as a potential prognostic marker for hepatocellular carcinoma. Clin. Chim. Acta 379, 127–133 (2007).
Umetani, N. et al. Prediction of breast tumor progression by integrity of free circulating DNA in serum. J. Clin. Oncol. 24, 4270–4276 (2006). First major study demonstrating a direct PCR assay for detecting ALU cfNA in patients with breast cancer. The study demonstrates that an ALU DNA integrity assay can be sensitive to detect early stage metastasis to regional tumour-draining lymph nodes.
Umetani, N. et al. Increased integrity of free circulating DNA in sera of patients with colorectal or periampullary cancer: direct quantitative PCR for ALU repeats. Clin. Chem. 52, 1062–1069 (2006).
Schulz, W. A., Steinhoff, C. & Florl, A. R. Methylation of endogenous human retroelements in health and disease. Curr. Top. Microbiol. Immunol. 310, 211–250 (2006).
Schwarzenbach, H. et al. Comparative evaluation of cell-free tumor DNA in blood and disseminated tumor cells in bone marrow of patients with primary breast cancer. Breast Cancer Res. 11, R71 (2009). First study indicating that tumour cfDNA may stem at least partly from DTCs in bone marrow.
Silva, J. M. et al. Tumor DNA in plasma at diagnosis of breast cancer patients is a valuable predictor of disease-free survival. Clin. Cancer Res. 8, 3761–3766 (2002).
Taback, B. et al. Detection of tumor-specific genetic alterations in bone marrow from early-stage breast cancer patients. Cancer Res. 63, 1884–1887 (2003).
Bruhn, N. et al. Detection of microsatellite alterations in the DNA isolated from tumor cells and from plasma DNA of patients with lung cancer. Ann. N. Y Acad. Sci. 906, 72–82 (2000).
Sozzi, G. et al. Analysis of circulating tumor DNA in plasma at diagnosis and during follow-up of lung cancer patients. Cancer Res. 61, 4675–4678 (2001).
Sunami, E. et al. Multimarker circulating DNA assay for assessing blood of prostate cancer patients. Clin. Chem. 55, 559–567 (2009).
Coulet, F. et al. Detection of plasma tumor DNA in head and neck squamous cell carcinoma by microsatellite typing and p53 mutation analysis. Cancer Res. 60, 707–711 (2000).
Hibi, K. et al. Molecular detection of genetic alterations in the serum of colorectal cancer patients. Cancer Res. 58, 1405–1407 (1998).
Kopreski, M. S. et al. Detection of mutant K-ras DNA in plasma or serum of patients with colorectal cancer. Br. J. Cancer 76, 1293–1299 (1997).
Schulte-Hermann, R. et al. Role of active cell death (apoptosis) in multi-stage carcinogenesis. Toxicol. Lett. 82–83, 143–148 (1995).
De Roock, W., Biesmans, B., De Schutter, J. & Tejpar, S. Clinical biomarkers in oncology: focus on colorectal cancer. Mol. Diagn. Ther. 13, 103–114 (2009).
Downward, J. Targeting RAS signalling pathways in cancer therapy. Nature Rev. Cancer 3, 11–22 (2003).
Levine, A. J. & Oren, M. The first 30 years of p53: growing ever more complex. Nature Rev. Cancer 9, 749–758 (2009).
Castells, A. et al. K-ras mutations in DNA extracted from the plasma of patients with pancreatic carcinoma: diagnostic utility and prognostic significance. J. Clin. Oncol. 17, 578–584 (1999).
Ryan, B. M. et al. A prospective study of circulating mutant KRAS2 in the serum of patients with colorectal neoplasia: strong prognostic indicator in postoperative follow up. Gut 52, 101–108 (2003).
Wang, S. et al. Potential clinical significance of a plasma-based KRAS mutation analysis in patients with advanced non-small cell lung cancer. Clin. Cancer Res. 16, 1324–1330 (2010).
Shinozaki, M. et al. Utility of circulating B-RAF DNA mutation in serum for monitoring melanoma patients receiving biochemotherapy. Clin. Cancer Res. 13, 2068–2074 (2007). This is the first major study to demonstrate circulating BRAF DNA mutation in patients with different stages of melanoma, and that cfDNA mutation detection has clinical utility for monitoring patient responses before and after therapy.
Flaherty, K. T. et al. Inhibition of mutated, activated BRAF in metastatic melanoma. N. Engl. J. Med. 363, 809–819 (2010).
Kefford, R. et al. Phase I/II study of GSK2118436, a selective inhibitor of oncogenic mutant BRAF kinase, in patients with metastatic melanoma and other solid tumors. J. Clin. Oncol. 28, 8503 (2010).
Ciardiello, F. & Tortora, G. EGFR antagonists in cancer treatment. N. Engl. J. Med. 358, 1160–1174 (2008).
Kimura, H. et al. EGFR mutation status in tumour-derived DNA from pleural effusion fluid is a practical basis for predicting the response to gefitinib. Br. J. Cancer 95, 1390–1395 (2006).
Kobayashi, S. et al. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N. Engl. J. Med. 352, 786–792 (2005).
Bennett, E. A. et al. Active Alu retrotransposons in the human genome. Genome Res. 18, 1875–1883 (2008).
Wolff, E. M. et al. Hypomethylation of a LINE-1 promoter activates an alternate transcript of the MET oncogene in bladders with cancer. PLoS Genet. 6, e1000917 (2010).
Chan, K. C., Leung, S. F., Yeung, S. W., Chan, A. T. & Lo, Y. M. Persistent aberrations in circulating DNA integrity after radiotherapy are associated with poor prognosis in nasopharyngeal carcinoma patients. Clin. Cancer Res. 14, 4141–4145 (2008).
Ellinger, J. et al. Cell-free circulating DNA: diagnostic value in patients with testicular germ cell cancer. J. Urol. 181, 363–371 (2009).
Salani, R. et al. Measurement of cyclin E genomic copy number and strand length in cell-free DNA distinguish malignant versus benign effusions. Clin. Cancer Res. 13, 5805–5809 (2007).
Klose, R. J. & Bird, A. P. Genomic DNA methylation: the mark and its mediators. Trends Biochem. Sci. 31, 89–97 (2006).
Kristensen, L. S. & Hansen, L. L. PCR-based methods for detecting single-locus DNA methylation biomarkers in cancer diagnostics, prognostics, and response to treatment. Clin. Chem. 55, 1471–1483 (2009).
Ellinger, J. et al. CpG island hypermethylation in cell-free serum DNA identifies patients with localized prostate cancer. Prostate 68, 42–49 (2008).
Taback, B., Saha, S. & Hoon, D. S. Comparative analysis of mesenteric and peripheral blood circulating tumor DNA in colorectal cancer patients. Ann. N. Y Acad. Sci. 1075, 197–203 (2006).
Lane, A. A. & Chabner, B. A. Histone deacetylase inhibitors in cancer therapy. J. Clin. Oncol. 27, 5459–5468 (2009).
Cameron, E. E., Bachman, K. E., Myohanen, S., Herman, J. G. & Baylin, S. B. Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer. Nature Genet. 21, 103–107 (1999).
Laktionov, P. P. et al. Cell-surface-bound nucleic acids: free and cell-surface-bound nucleic acids in blood of healthy donors and breast cancer patients. Ann. N. Y Acad. Sci. 1022, 221–227 (2004).
Holdenrieder, S. et al. Nucleosomes in serum of patients with benign and malignant diseases. Int. J. Cancer 95, 114–120 (2001).
Roth, C. et al. Apoptosis-related deregulation of proteolytic activities and high serum levels of circulating nucleosomes and DNA in blood correlate with breast cancer progression. BMC Cancer 11, 4 (2010).
Holdenrieder, S. et al. Clinical relevance of circulating nucleosomes in cancer. Ann. N. Y Acad. Sci. 1137, 180–189 (2008).
Lo, Y. M. et al. Molecular prognostication of nasopharyngeal carcinoma by quantitative analysis of circulating Epstein-Barr virus DNA. Cancer Res. 60, 6878–6881 (2000).
Kim, B. K. et al. Persistent hepatitis B viral replication affects recurrence of hepatocellular carcinoma after curative resection. Liver Int. 28, 393–401 (2008).
Illades-Aguiar, B. et al. Prevalence and distribution of human papillomavirus types in cervical cancer, squamous intraepithelial lesions, and with no intraepithelial lesions in women from Southern Mexico. Gynecol. Oncol. 117, 291–296 (2010).
Yu, K. H. et al. Quantitative analysis of cell-free Epstein-Barr virus DNA in plasma of patients with nonnasopharyngeal head and neck carcinomas. Clin. Cancer Res. 10, 1726–1732 (2004).
Chan, A. T. et al. Plasma Epstein-Barr virus DNA and residual disease after radiotherapy for undifferentiated nasopharyngeal carcinoma. J. Natl Cancer Inst. 94, 1614–1619 (2002).
Leung, S. F. et al. Plasma Epstein-Barr viral deoxyribonucleic acid quantitation complements tumor-node-metastasis staging prognostication in nasopharyngeal carcinoma. J. Clin. Oncol. 24, 5414–5418 (2006). This study describes the use of plasma EBV in nasopharyngeal carcinoma (NPC) prognostication and monitoring during therapy. Pretherapy circulating EBV DNA level was shown to be an independent prognostic factor in NPC.
Lin, J. C. et al. Quantification of plasma Epstein-Barr virus DNA in patients with advanced nasopharyngeal carcinoma. N. Engl. J. Med. 350, 2461–2470 (2004).
Lo, Y. M. et al. Quantitative analysis of cell-free Epstein-Barr virus DNA in plasma of patients with nasopharyngeal carcinoma. Cancer Res. 59, 1188–1191 (1999). This study describes detection of circulating EBV DNA in patients with NPC and provides evidence that this approach can be used for the monitoring and early detection of NPC.
Lo, Y. M. et al. Plasma cell-free Epstein-Barr virus DNA quantitation in patients with nasopharyngeal carcinoma. Correlation with clinical staging. Ann. N. Y Acad. Sci. 906, 99–101 (2000).
Ji, M. F. et al. Detection of Stage I nasopharyngeal carcinoma by serologic screening and clinical examination. Chin. J. Cancer 30, 120–123 (2011).
Garcia-Olmo, D. C., Ruiz-Piqueras, R. & Garcia-Olmo, D. Circulating nucleic acids in plasma and serum (CNAPS) and its relation to stem cells and cancer metastasis: state of the issue. Histol. Histopathol. 19, 575–583 (2004).
Garcia-Olmo, D. C. et al. Cell-free nucleic acids circulating in the plasma of colorectal cancer patients induce the oncogenic transformation of susceptible cultured cells. Cancer Res. 70, 560–567 (2010).
Sturgeon, C. M. & Diamandis, E. P. Use of tumor markers in clinical practice: quality requirements. Clin. Physiol. Biochem. 1–37 (2008).
Bustin, S. A. et al. The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin. Chem. 55, 611–622 (2009).
Orozco, A. F. & Lewis, D. E. Flow cytometric analysis of circulating microparticles in plasma. Cytometry A 77, 502–514 (2010).
Cocucci, E., Racchetti, G. & Meldolesi, J. Shedding microvesicles: artefacts no more. Trends Cell Biol. 19, 43–51 (2009).
O'Driscoll, L. et al. Feasibility and relevance of global expression profiling of gene transcripts in serum from breast cancer patients using whole genome microarrays and quantitative RT-PCR. Cancer Genomics Proteomics 5, 94–104 (2008).
Barzon, L., Boscaro, M., Pacenti, M., Taccaliti, A. & Palu, G. Evaluation of circulating thyroid-specific transcripts as markers of thyroid cancer relapse. Int. J. Cancer 110, 914–920 (2004).
Lombardi, C. P. et al. Circulating thyroglobulin mRNA does not predict early and midterm recurrences in patients undergoing thyroidectomy for cancer. Am. J. Surg. 196, 326–332 (2008).
Garcia, V. et al. Free circulating mRNA in plasma from breast cancer patients and clinical outcome. Cancer Lett. 263, 312–320 (2008).
Wong, B. C. et al. Reduced plasma RNA integrity in nasopharyngeal carcinoma patients. Clin. Cancer Res. 12, 2512–2516 (2006).
Miura, N. et al. Clinical usefulness of serum telomerase reverse transcriptase (hTERT) mRNA and epidermal growth factor receptor (EGFR) mRNA as a novel tumor marker for lung cancer. Cancer Sci. 97, 1366–1373 (2006).
Kosaka, N., Iguchi, H. & Ochiya, T. Circulating microRNA in body fluid: a new potential biomarker for cancer diagnosis and prognosis. Cancer Sci. 101, 2087–2092 (2010).
Mitchell, P. S. et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc. Natl Acad. Sci. USA 105, 10513–10518 (2008). This is the first major study describing the detection of circulating miRNAs in both plasma and serum, and their use in assessing patients with prostate cancer.
Schaefer, A. et al. Suitable reference genes for relative quantification of miRNA expression in prostate cancer. Exp. Mol. Med. 42, 749–758 (2010).
Mestdagh, P. et al. A novel and universal method for microRNA RT-qPCR data normalization. Genome Biol. 10, R64 (2009).
Heneghan, H. M., Miller, N., Lowery, A. J., Sweeney, K. J. & Kerin, M. J. MicroRNAs as novel biomarkers for breast cancer. J. Oncol. 2009, 950201 (2009).
Lawrie, C. H. et al. Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br. J. Haematol. 141, 672–675 (2008). The presence of miRNAs in serum was first described for cancer patients in this paper.
Roth, C., Kasimir-Bauer, S., Heubner, M., Pantel, K. & Schwarzenbach, H. Circulating Nucleic Acids in Plasma and Serum. 63–71 (Springer, 2011).
Roth, C. et al. Circulating microRNAs as blood-based markers for patients with primary and metastatic breast cancer. Breast Cancer Res. 12, R90 (2010).
Ng, E. K. et al. Differential expression of microRNAs in plasma of patients with colorectal cancer: a potential marker for colorectal cancer screening. Gut 58, 1375–1381 (2009).
Asaga, S. et al. Direct serum assay for microRNA-21 concentrations in early and advanced breast cancer. Clin. Chem. 57, 84–91 (2011). This study demonstrates the development of a direct blood PCR assay for detection of circulating miR-21 and its ability to assess early stage breast cancer in serum.
Hu, Z. et al. Serum microRNA signatures identified in a genome-wide serum microRNA expression profiling predict survival of non-small-cell lung cancer. J. Clin. Oncol. 28, 1721–1726 (2010). This article describes the first major study on the use of a panel of circulating miRNAs in serum to predict overall survival outcome in NSCLC.
Yamamoto, Y. et al. MicroRNA-500 as a potential diagnostic marker for hepatocellular carcinoma. Biomarkers 14, 529–538 (2009).
Pantel, K. & Alix-Panabieres, C. Circulating tumour cells in cancer patients: challenges and perspectives. Trends Mol. Med. 16, 398–406 (2010).
Pantel, K., Brakenhoff, R. H. & Brandt, B. Detection, clinical relevance and specific biological properties of disseminating tumour cells. Nature Rev. Cancer 8, 329–340 (2008).
Schwarzenbach, H. & Pantel, K. Methods of Cancer Diagnosis, Therapy and Prognosis. 481–497 (Springer, USA, 2008).
Nawroz-Danish, H. et al. Microsatellite analysis of serum DNA in patients with head and neck cancer. Int. J. Cancer 111, 96–100 (2004).
Koyanagi, K. et al. Association of circulating tumor cells with serum tumor-related methylated DNA in peripheral blood of melanoma patients. Cancer Res. 66, 6111–6117 (2006). This study indicates that a combined assessment of methylated cfDNA and CTCs in blood may be a useful determinant of disease status and efficacy of systemic therapy of metastatic melanoma.
Matuschek, C. et al. Methylated APC and GSTP1 genes in serum DNA correlate with the presence of circulating blood tumor cells and are associated with a more aggressive and advanced breast cancer disease. Eur. J. Med. Res. 15, 277–286 (2010).
Pinzani, P. et al. Tyrosinase mRNA levels in the blood of uveal melanoma patients: correlation with the number of circulating tumor cells and tumor progression. Melanoma Res. 20, 303–310 (2010).
Van der Auwera, I. et al. The presence of circulating total DNA and methylated genes is associated with circulating tumour cells in blood from breast cancer patients. Br. J. Cancer 100, 1277–1286 (2009).
Mori, T. et al. Predictive utility of circulating methylated DNA in serum of melanoma patients receiving biochemotherapy. J. Clin. Oncol. 23, 9351–9358 (2005). This was the first study to demonstrate that hypermethylation of cfDNA in patients with melanoma relates to tumour progression and response to therapy, and that a panel of methylated tumour-related cfDNA can be of prognostic value before therapy.
Diehl, F. et al. Circulating mutant DNA to assess tumor dynamics. Nature Med. 14, 985–990 (2008). This article describes a new highly sensitive approach to quantify cfDNA which was applied to monitor chemotherapy.
Esteller, M. & Herman, J. G. Cancer as an epigenetic disease: DNA methylation and chromatin alterations in human tumours. J. Pathol. 196, 1–7 (2002).
Hendrich, B. & Tweedie, S. The methyl-CpG binding domain and the evolving role of DNA methylation in animals. Trends Genet. 19, 269–277 (2003).
Zheng, Y. G., Wu, J., Chen, Z. & Goodman, M. Chemical regulation of epigenetic modifications: opportunities for new cancer therapy. Med. Res. Rev. 28, 645–687 (2008).
Cedar, H. & Bergman, Y. Linking DNA methylation and histone modification: patterns and paradigms. Nature Rev. Genet. 10, 295–304 (2009).
Croce, C. M. Causes and consequences of microRNA dysregulation in cancer. Nature Rev. Genet. 10, 704–714 (2009).
Ellinger, J. et al. Apoptotic DNA fragments in serum of patients with muscle invasive bladder cancer: a prognostic entity. Cancer Lett. 264, 274–280 (2008).
Valenzuela, M. T. et al. Assessing the use of p16INK4α promoter gene methylation in serum for detection of bladder cancer. Eur. Urol. 42, 622–628; discussion 628–30 (2002).
Utting, M., Werner, W., Dahse, R., Schubert, J. & Junker, K. Microsatellite analysis of free tumor DNA in urine, serum, and plasma of patients: a minimally invasive method for the detection of bladder cancer. Clin. Cancer Res. 8, 35–40 (2002).
Fiegl, H. et al. Circulating tumor-specific DNA: a marker for monitoring efficacy of adjuvant therapy in cancer patients. Cancer Res. 65, 1141–1145 (2005).
Rykova, E. Y. et al. Extracellular DNA in breast cancer: cell-surface-bound, tumor-derived extracellular DNA in blood of patients with breast cancer and nonmalignant tumors. Ann. N. Y Acad. Sci. 1022, 217–220 (2004).
Sharma, G. et al. CpG hypomethylation of MDR1 gene in tumor and serum of invasive ductal breast carcinoma patients. Clin. Biochem. 43, 373–379 (2010).
Sharma, G. et al. Clinical significance of promoter hypermethylation of DNA repair genes in tumor and serum DNA in invasive ductal breast carcinoma patients. Life Sci. 87, 83–91 (2010).
Skvortsova, T. E. et al. Cell-free and cell-bound circulating DNA in breast tumours: DNA quantification and analysis of tumour-related gene methylation. Br. J. Cancer 94, 1492–1495 (2006).
Deligezer, U. et al. Effect of adjuvant chemotherapy on integrity of free serum DNA in patients with breast cancer. Ann. N. Y Acad. Sci. 1137, 175–179 (2008).
Kohler, C. et al. Levels of plasma circulating cell free nuclear and mitochondrial DNA as potential biomarkers for breast tumors. Mol. Cancer 8, 105 (2009).
Ren, C. C. et al. Methylation status of the fragile histidine triad and E-cadherin genes in plasma of cervical cancer patients. Int. J. Gynecol. Cancer 16, 1862–1867 (2006).
Widschwendter, A. et al. DNA methylation in serum and tumors of cervical cancer patients. Clin. Cancer Res. 10, 565–571 (2004).
Pornthanakasem, W. et al. Human papillomavirus DNA in plasma of patients with cervical cancer. BMC Cancer 1, 2 (2001).
Lecomte, T. et al. Detection of free-circulating tumor-associated DNA in plasma of colorectal cancer patients and its association with prognosis. Int. J. Cancer 100, 542–548 (2002).
Lefebure, B. et al. Prognostic value of circulating mutant DNA in unresectable metastatic colorectal cancer. Ann. Surg. 251, 275–280 (2010).
Trevisiol, C. et al. Prognostic value of circulating KRAS2 gene mutations in colorectal cancer with distant metastases. Int. J. Biol. Markers 21, 223–228 (2006).
Wang, J. Y. et al. Molecular detection of APC, K- ras, and p53 mutations in the serum of colorectal cancer patients as circulating biomarkers. World J. Surg. 28, 721–726 (2004).
deVos, T. et al. Circulating methylated SEPT9 DNA in plasma is a biomarker for colorectal cancer. Clin. Chem. 55, 1337–1346 (2009).
Grutzmann, R. et al. Sensitive detection of colorectal cancer in peripheral blood by septin 9 DNA methylation assay. PLoS ONE 3, e3759 (2008). This was the first study that demonstarated the clinical use of methylated cfDNA as a specific plasma biomarker for screening colorectal cancer.
He, Q. et al. Development of a multiplex MethyLight assay for the detection of multigene methylation in human colorectal cancer. Cancer Genet. Cytogenet. 202, 1–10 (2010).
Tanzer, M. et al. Performance of epigenetic markers SEPT9 and ALX4 in plasma for detection of colorectal precancerous lesions. PLoS ONE 5, e9061 (2010).
Chan, K. C. et al. Quantitative analysis of circulating methylated DNA as a biomarker for hepatocellular carcinoma. Clin. Chem. 54, 1528–1536 (2008).
Wang, J., Qin, Y., Li, B., Sun, Z. & Yang, B. Detection of aberrant promoter methylation of GSTP1 in the tumor and serum of Chinese human primary hepatocellular carcinoma patients. Clin. Biochem. 39, 344–348 (2006).
Wong, I. H., Lo, Y. M., Yeo, W., Lau, W. Y. & Johnson, P. J. Frequent p15 promoter methylation in tumor and peripheral blood from hepatocellular carcinoma patients. Clin. Cancer Res. 6, 3516–3521 (2000).
Ren, N. et al. The prognostic value of circulating plasma DNA level and its allelic imbalance on chromosome 8p in patients with hepatocellular carcinoma. J. Cancer Res. Clin. Oncol. 132, 399–407 (2006).
Szymanska, K. et al. Ser-249TP53 mutation in tumour and plasma DNA of hepatocellular carcinoma patients from a high incidence area in the Gambia, West Africa. Int. J. Cancer 110, 374–379 (2004).
Kirk, G. D. et al. 249ser TP53 mutation in plasma DNA, hepatitis B viral infection, and risk of hepatocellular carcinoma. Oncogene 24, 5858–5867 (2005).
Su, Y. W., Huang, Y. W., Chen, S. H. & Tzen, C. Y. Quantitative analysis of plasma HBV DNA for early evaluation of the response to transcatheter arterial embolization for HBV-related hepatocellular carcinoma. World J. Gastroenterol. 11, 6193–6196 (2005).
Gautschi, O. et al. Origin and prognostic value of circulating KRAS mutations in lung cancer patients. Cancer Lett. 254, 265–273 (2007).
Jian, G. et al. Prediction of epidermal growth factor receptor mutations in the plasma/pleural effusion to efficacy of gefitinib treatment in advanced non-small cell lung cancer. J. Cancer Res. Clin. Oncol. 136, 1341–1347 (2010).
An, Q. et al. Detection of p16 hypermethylation in circulating plasma DNA of non-small cell lung cancer patients. Cancer Lett. 188, 109–114 (2002).
Bearzatto, A. et al. p16INK4A Hypermethylation detected by fluorescent methylation-specific PCR in plasmas from non-small cell lung cancer. Clin. Cancer Res. 8, 3782–3787 (2002).
Liu, Y. et al. Hypermethylation of p16INK4α in Chinese lung cancer patients: biological and clinical implications. Carcinogenesis 24, 1897–1901 (2003).
Ng, C. S. et al. Tumor p16M is a possible marker of advanced stage in non-small cell lung cancer. J. Surg. Oncol. 79, 101–106 (2002).
Ramirez, J. L. et al. 14-3-3sigma methylation in pretreatment serum circulating DNA of cisplatin-plus-gemcitabine-treated advanced non-small-cell lung cancer patients predicts survival: The Spanish Lung Cancer Group. J. Clin. Oncol. 23, 9105–9112 (2005).
Hosny, G., Farahat, N. & Hainaut, P. TP53 mutations in circulating free DNA from Egyptian patients with non-Hodgkin's lymphoma. Cancer Lett. 275, 234–239 (2009).
Au, W. Y., Pang, A., Choy, C., Chim., C. S. & Kwong, Y. L. Quantification of circulating Epstein-Barr virus (EBV) DNA in the diagnosis and monitoring of natural killer cell and EBV-positive lymphomas in immunocompetent patients. Blood 104, 243–249 (2004).
Lei, K. I., Chan, L. Y., Chan, W. Y., Johnson, P. J. & Lo, Y. M. Diagnostic and prognostic implications of circulating cell-free Epstein-Barr virus DNA in natural killer/T-cell lymphoma. Clin. Cancer Res. 8, 29–34 (2002).
Machado, A. S. et al. Circulating cell-free and Epstein-Barr virus DNA in pediatric B-non-Hodgkin lymphomas. Leuk. Lymphoma 51, 1020–1027 (2010).
Deligezer, U., Yaman, F., Erten, N. & Dalay, N. Frequent copresence of methylated DNA and fragmented nucleosomal DNA in plasma of lymphoma patients. Clin. Chim. Acta 335, 89–94 (2003).
Board, R. E. et al. Detection of BRAF mutations in the tumour and serum of patients enrolled in the AZD6244 (ARRY-142886) advanced melanoma phase II study. Br. J. Cancer 101, 1724–1730 (2009).
Pinzani, P. et al. Allele specific Taqman-based real-time PCR assay to quantify circulating BRAFV600E mutated DNA in plasma of melanoma patients. Clin. Chim. Acta 411, 1319–1324 (2010).
Fujimoto, A., O'Day, S. J., Taback, B., Elashoff, D. & Hoon, D. S. Allelic imbalance on 12q22–23 in serum circulating DNA of melanoma patients predicts disease outcome. Cancer Res. 64, 4085–4088 (2004).
Fujiwara, Y. et al. Plasma DNA microsatellites as tumor-specific markers and indicators of tumor progression in melanoma patients. Cancer Res. 59, 1567–1571 (1999).
Taback, B. et al. Prognostic significance of circulating microsatellite markers in the plasma of melanoma patients. Cancer Res. 61, 5723–5726 (2001).
Taback, B. et al. Circulating DNA microsatellites: molecular determinants of response to biochemotherapy in patients with metastatic melanoma. J. Natl Cancer Inst. 96, 152–156 (2004).
Melnikov, A., Scholtens, D., Godwin, A. & Levenson, V. Differential methylation profile of ovarian cancer in tissues and plasma. J. Mol. Diagn. 11, 60–65 (2009).
Muller, H. M. et al. Analysis of methylated genes in peritoneal fluids of ovarian cancer patients: a new prognostic tool. Clin. Chem. 50, 2171–2173 (2004).
Swisher, E. M. et al. Tumor-specific p53 sequences in blood and peritoneal fluid of women with epithelial ovarian cancer. Am. J. Obstet. Gynecol. 193, 662–667 (2005).
Zachariah, R. R. et al. Levels of circulating cell-free nuclear and mitochondrial DNA in benign and malignant ovarian tumors. Obstet. Gynecol. 112, 843–850 (2008).
Liggett, T. et al. Differential methylation of cell-free circulating DNA among patients with pancreatic cancer versus chronic pancreatitis. Cancer 116, 1674–1680 (2010).
Melnikov, A. A., Scholtens, D., Talamonti, M. S., Bentrem, D. J. & Levenson, V. V. Methylation profile of circulating plasma DNA in patients with pancreatic cancer. J. Surg. Oncol. 99, 119–122 (2009).
Bastian, P. J. et al. Preoperative serum DNA GSTP1 CpG island hypermethylation and the risk of early prostate-specific antigen recurrence following radical prostatectomy. Clin. Cancer Res. 11, 4037–4043 (2005).
Bryzgunova, O. E., Morozkin, E. S., Yarmoschuk, S. V., Vlassov, V. V. & Laktionov, P. P. 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, 222–225 (2008).
Goessl, C., Muller, M., Heicappell, R., Krause, H. & Miller, K. DNA-based detection of prostate cancer in blood, urine, and ejaculates. Ann. N. Y Acad. Sci. 945, 51–58 (2001).
Jeronimo, C. et al. Quantitative GSTP1 hypermethylation in bodily fluids of patients with prostate cancer. Urology 60, 1131–1135 (2002).
Roupret, M. et al. Promoter hypermethylation in circulating blood cells identifies prostate cancer progression. Int. J. Cancer 122, 952–956 (2008).
Ellinger, J. et al. Noncancerous PTGS2 DNA fragments of apoptotic origin in sera of prostate cancer patients qualify as diagnostic and prognostic indicators. Int. J. Cancer 122, 138–143 (2008).
Ellinger, J., Muller, S. C., Wernert, N., von Ruecker, A. & Bastian, P. J. Mitochondrial DNA in serum of patients with prostate cancer: a predictor of biochemical recurrence after prostatectomy. BJU Int. 102, 628–632 (2008).