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Use of DNA Methylation for Cancer Detection and Molecular Classification

  • Zhu, Jingde (Cancer Genetics and Gene Therapy program, The State-key Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiaotong University) ;
  • Yao, Xuebiao (Division of Cellular Dynamics, Hefei National Laboratory)
  • Published : 2007.03.31

Abstract

Conjugation of the methyl group at the fifth carbon of cytosines within the palindromic dinucleotide 5'-CpG-3' sequence (DNA methylation) is the best studied epigenetic mechanism, which acts together with other epigenetic entities: histone modification, chromatin remodeling and microRNAs to shape the chromatin structure of DNA according to its functional state. The cancer genome is frequently characterized by hypermethylation of specific genes concurrently with an overall decrease in the level of 5-methyl cytosine, the pathological implication of which to the cancerous state has been well established. While the latest genome-wide technologies have been applied to classify and interpret the epigenetic layer of gene regulation in the physiological and disease states, the epigenetic testing has also been seriously explored in clinical practice for early detection, refining tumor staging and predicting disease recurrence. This critique reviews the latest research findings on the use of DNA methylation in cancer diagnosis, prognosis and staging/classification.

Keywords

References

  1. Baylin, S. B. and Ohm, J. E. (2006) Epigenetic gene silencing in cancer - a mechanism for early oncogenic pathway addiction? Nat. Rev. Cancer 6, 107-116. https://doi.org/10.1038/nrc1799
  2. Belinsky, S. A. (2004) Gene-promoter hypermethylation as a biomarker in lung cancer. Nat. Rev. Cancer 4, 707-717. https://doi.org/10.1038/nrc1432
  3. Belinsky, S. A., Nikula, K. J., Palmisano, W. A., Michels, R., Saccomanno, G.., Gabrielson, E., Baylin, S. B. and Herman, J. G. (1998) Aberrant methylation of p16(INK4a) is an early event in lung cancer and a potential biomarker for early diagnosis. Proc. Nat. Acad. Sci. USA 95, 11891-11896. https://doi.org/10.1073/pnas.95.20.11891
  4. Bird, A. (1992) The essentials of DNA methylation. Cell 70, 5-8. https://doi.org/10.1016/0092-8674(92)90526-I
  5. Bird, A. P. (1986) CpG-rich islands and the function of DNA methylation. Nature 321, 209-213. https://doi.org/10.1038/321209a0
  6. Chen, J. X., Zheng, Y., West, M. and Tang, M. S. (1998) Carcinogens preferentially bind at methylated CpG in the p53 mutational hot spots. Cancer Res. 58, 2070-2075.
  7. Cui, H., Cruz-Correa, M., Giardiello, F. M., Hutcheon, D. F., Kafonek, D. R., Brandenburg, S., Wu, Y., He, X., Powe, N. R. and Feinberg, A. P. (2003) Loss of IGF2 imprinting: a potential marker of colorectal cancer risk. Sci. 299, 1753-1755. https://doi.org/10.1126/science.1080902
  8. Ding, S., Gong, B. D., Yu, J., Gu, J., Zhang, H. Y., Shang, Z. B., Fei, Q., Wang, P. and Zhu, J. D. (2004) Methylation profile of the promoter CpG islands of 14 'drug-resistance' genes in hepatocellular carcinoma. World J. Gastroenterol. 10, 3433-3440. https://doi.org/10.3748/wjg.v10.i23.3433
  9. Eads, C. A., Danenberg, K. D., Kawakami, K., Saltz, L. B., Blake, C., Shibata, D., Danenberg, P. V. and Laird, P. W. (2000) MethyLight: a high-throughput assay to measure DNA methylation. Nucleic Acid Res. 28, 32. https://doi.org/10.1093/nar/28.8.e32
  10. Eden, A., Gaudet, F., Waghmare, A. and Jaenisch, R. (2003) Chromosomal instability and tumors promoted by DNA hypomethylation. Science 300, 455. https://doi.org/10.1126/science.1083557
  11. Esteller, M. (2000) Epigenetic lesions causing genetic lesions in human cancer: promoter hypermethylation of DNA repair genes. Eur. J .Cancer 36, 2294-2300. https://doi.org/10.1016/S0959-8049(00)00303-8
  12. Esteller, M., Fraga, M. F., Guo, M., Garcia-Foncillas, J., Hedenfalk, I., Godwin, A. K., Trojan, J., Vaurs-Barriere, C., Bignon, Y. J., Ramus, S., Benitez, J., Caldes, T., Akiyama, Y., Yuasa, Y., Launonen, V., Canal, M. J., Rodriguez, R., Capella, G., Peinado, M. A., Borg, A., Aaltonen, L. A., Ponder, B. A., Baylin, S. B. and Herman, J. G. (2001) DNA methylation patterns in hereditary human cancers mimic sporadic tumorigenesis. Hum. Mol. Genet. 10, 3001-3007. https://doi.org/10.1093/hmg/10.26.3001
  13. Esteller, M., Risques, R. A., Toyota, M., Capella, G., Moreno, V., Peinado, M. A., Baylin, S. B. and Herman, J. G. (2001) Promoter hypermethylation of the DNA repair gene O(6)-methylguanine-DNA methyltransferase is associated with the presence of G:C to A:T transition mutations in p53 in human colorectal tumorigenesis. Cancer Res. 61, 4689-4692.
  14. Gaudet, F., Hodgson, J. G., Eden, A., Jackson-Grusby, L., Dausman, J., Gray, J. W., Leonhardt, H. and Jaenisch, R. (2003) Induction of tumors in mice by genomic hypomethylation. Science 300, 489-492. https://doi.org/10.1126/science.1083558
  15. Gospodarowicz, M. K., Miller, D., Groome, P. A., Greene, F. L., Logan, P. A. and Sobin, L. H. (2004) The process for continuous improvement of the TNM classification. Cancer 100, 1-5. https://doi.org/10.1002/cncr.11898
  16. Gu, L., Yu, J., Fei, Q., Zhang, H., Xu, H., Gu, J., Zhu, T. and Zhu J. (2006) The promoter CpG island of the anti-apoptotic gene, BCL2 is hypermethylated in urine sediments of 28.3% bladder cancer patients. Tumor(China) 26, 497-601.
  17. Hanahan, D. and Weinberg, R. A. (2000) The hallmarks of cancer. Cell 100, 57-70. https://doi.org/10.1016/S0092-8674(00)81683-9
  18. Herman, J. G., Graff, J. R., Myohanen, S., Nelkin, B. D. and Baylin, S. B. (1996) Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc. Natl. Acad. Sci. USA 93, 9821-9826. https://doi.org/10.1073/pnas.93.18.9821
  19. Holm, T. M., Jackson-Grusby, L., Brambrink, T., Yamada, Y., Rideout, W. M., 3rd and Jaenisch, R. (2005) Global loss of imprinting leads to widespread tumorigenesis in adult mice. Cancer Cell 8, 275-285. https://doi.org/10.1016/j.ccr.2005.09.007
  20. Huang, J., Zhang, X., Zhang, M., Zhu, J., Zhang, Y., Lin, Y., Wang, K., Qi, X., Zhang, Q., Liu, G., Yu, J., Cui, Y., Yang, P., Wang, Z. and Han, Z. (2006) Recurrence of DLK1 as an imprimted gene could contribute to human hepatcocellular carcinoma. Carcinogenesis in press.
  21. Jaenisch, R. and Bird, A. (2003) Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat. Genet. 33, 245-254. https://doi.org/10.1038/ng1089
  22. Janzen, V., Forkert, R., Fleming, H. E., Saito, Y., Waring, M. T., Dombkowski, D. M., Cheng, T., DePinho, R. A., Sharpless, N. E. and Scadden, D. T. (2006) Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a. Nature 443, 421-426. https://doi.org/10.1038/nature05159
  23. Jelinic, P. and Shaw, P. (2007) Loss of imprinting and cancer. J. Pathol. 211, 261-268. https://doi.org/10.1002/path.2116
  24. Jubb, A. M., Quirke, P. and Oates, A. J. (2003) DNA methylation, a biomarker for colorectal cancer: implications for screening and pathological utility. Ann. N. Y. Acad. Sci. 983, 251-267. https://doi.org/10.1111/j.1749-6632.2003.tb05980.x
  25. Kinzler, K. W. and Vogelstein, B. (1996) Lessons from hereditary colorectal cancer. Cell 87, 159-170. https://doi.org/10.1016/S0092-8674(00)81333-1
  26. Kolble, K., Ullrich, O. M., Pidde, H., Barthel, B., Diermann, J., Rudolph, B., Dietel, M., Schlag, P. M. and Scherneck, S. (1999) Microsatellite alterations in serum DNA of patients with colorectal cancer. Lab. Invest. 79, 1145-1150.
  27. Li, J., Fei Q., Yu, J., Zhang, H., Wang, P. and Zhu, J. (2004) The methylation state of the promoter CpG islands of seven metastasis-associated genes and their expression state in six cell lines of liver origins. Chin. J. Cancer 23, 1-7.
  28. Macdonald, J. S. (1999) Carcinoembryonic antigen screening: pros and cons. Semin. oncology 26, 556-560.
  29. Palmisano, W. A., Divine, K. K., Saccomanno, G., Gilliland, F. D., Baylin, S. B., Herman, J. G. and Belinsky, S. A. (2000) Predicting lung cancer by detecting aberrant promoter methylation in sputum. Cancer Res. 60, 5954-5958.
  30. Radtke, F. and Clevers, H. (2005) Self-renewal and cancer of the gut: two sides of a coin. Sci. 307, 1904-1909. https://doi.org/10.1126/science.1104815
  31. Rakyan, V. K., Hildmann, T., Novik, K. L., Lewin, J., Tost, J., Cox, A. V., Andrews, T. D., Howe, K. L., Otto, T., Olek, A., Fischer, J., Gut, I. G., Berlin, K. and Beck, S. (2004) DNA methylation profiling of the human major histocompatibility complex: a pilot study for the human epigenome project. PLos. Biol 2, e405. https://doi.org/10.1371/journal.pbio.0020405
  32. Reynolds, P. A., Sigaroudinia, M., Zardo, G., Wilson, M. B., Benton, G. M., Miller, C. J., Hong, C., Fridlyand, J., Costello, J. F. and Tlsty, T. D. (2006) Tumor suppressor p16INK4A regulates polycomb-mediated DNA hypermethylation in human mammary epithelial cells. J. Biol. Chem. 281, 24790-24802. https://doi.org/10.1074/jbc.M604175200
  33. Suzuki, H., Gabrielson, E., Chen, W., Anbazhagan, R., van Engeland, M., Weijenberg, M. P., Herman, J. G. and Baylin, S. B. (2002) A genomic screen for genes upregulated by demethylation and histone deacetylase inhibition in human colorectal cancer. Nat. Genet. 31, 141-149. https://doi.org/10.1038/ng892
  34. Suzuki, H., Watkins, D. N., Jair, K. W., Schuebel, K. E., Markowitz, S. D., Chen, W. D., Pretlow, T. P., Yang, B., Akiyama, Y., Van Engeland, M., Toyota, M., Tokino, T., Hinoda, Y., Imai, K., Herman, J. G. and Baylin, S. B. (2004) Epigenetic inactivation of SFRP genes allows constitutive WNT signaling in colorectal cancer. Nat. Genet. 36, 417-422. https://doi.org/10.1038/ng1330
  35. Ting, A. H., Jair, K. W., Schuebel, K. E. and Baylin, S. B. (2006) Differential requirement for DNA methyltransferase 1 in maintaining human cancer cell gene promoter hypermethylation. Cancer res. 66, 729-735. https://doi.org/10.1158/0008-5472.CAN-05-1537
  36. Tommasi, S., Denissenko, M. F. and Pfeifer, G. P. (1997) Sunlight induces pyrimidine dimers preferentially at 5-methylcytosine bases. Cancer Res. 57, 4727-4730.
  37. Trosko, J. E. and Upham, B. L. (2005) The emperor wears no clothes in the field of carcinogen risk assessment: ignored concepts in cancer risk assessment. Mutagenesis 20, 81-92. https://doi.org/10.1093/mutage/gei017
  38. Tsavellas, G., Patel, H. and Allen-Mersh, T. G. (2001) Detection and clinical significance of occult tumour cells in colorectal cancer. Br. J. Surg. 88, 1307-1320. https://doi.org/10.1046/j.0007-1323.2001.01863.x
  39. Ushijima, T., Nakajima, T. and Maekita, T. (2006) DNA methylation as a marker for the past and future. J. Gastroenterol. 41, 401-407. https://doi.org/10.1007/s00535-006-1846-6
  40. Xu, X., Yu, J., Zhang, H., Sun, M., Gu, J., Du, X., Sun, M., Shi, D., Wang, P., Yang, Z. and Zhu, J. (2004) Methylation profile of the promoter CpG islands of thirty one genes that may contribute to carcinogenesis of the colorectal cancer. World J. Gastroenterol. 10, 3441-3454. https://doi.org/10.3748/wjg.v10.i23.3441
  41. Xu, X. L., Yu, J., Zhang, H. Y., Sun, M. H., Gu, J., Du, X., Shi, D. R., Wang, P., Yang, Z. H. and Zhu, J. D. (2004) Methylation profile of the promoter CpG islands of 31 genes that may contribute to colorectal carcinogenesis. World J. Gastroenterol. 10, 3441-3454. https://doi.org/10.3748/wjg.v10.i23.3441
  42. Yang, Z., Shang, Z., Yu, J., Cai, Y., Zhang, H., Gu, J., Xu, H. and Zhu, J. (2004) The methylation profiles of the promoter CpG island of nine tumor associated genes correlate with their expression in three lung cancer cell lines. Tumor 11, 216-222.
  43. Yu, J., Ni, M., Xu, J., Zhang, H., Gao, B., Gu, J., Chen, J., Zhang, L., Wu, M., Zhen, S. and Zhu, J. (2002) Methylation profiling of twenty promoter-CpG islands of genes which may contribute to hepatocellular carcinogenesis. B.M.C. Cancer 2, 29. https://doi.org/10.1186/1471-2407-2-29
  44. Yu, J., Zhang, H., Gu, J., Lin, S., Li, J., Lu, W., Wang, Y. and Zhu, J. (2004) Methylation profiles of thirty four promoter CpG islands and concordant methylation behaviours of sixteen genes that may contribute to carcinogenesis of astrocytoma. B.M.C. Cancer 4, 65. https://doi.org/10.1186/1471-2407-4-65
  45. Yu, J., Zhang, H., Gu, J., Lin, S., Li, J., Lu, W., Wang, Y. and Zhu, J. (2004) Methylation profiling of thirty four promoter- CpG islands and concordant methylation behaviors of sixteen genes that may contribute to carcinogenesis of malignant glioma,. B.M.C Cancer 4, 65. https://doi.org/10.1186/1471-2407-4-65
  46. Yu, J., Zhang, H. Y., Ma, Z. Z., Lu, W., Wang, Y. F. and Zhu, J. D. (2003) Methylation profiling of twenty four genes and the concordant methylation behaviours of nineteen genes that may contribute to hepatocellular carcinogenesis. Cell Res. 13, 319-333. https://doi.org/10.1038/sj.cr.7290177
  47. Zhu, J. (2005) The altered DNA methylation pattern and its implications in liver cancer. Cell Res. 15, 272-280. https://doi.org/10.1038/sj.cr.7290296
  48. Zhu, J. (2006) DNA methylation and hepatocellular carcinoma. J. Hepatobiliary Pancreat Surg. 13, 265-273. https://doi.org/10.1007/s00534-005-1054-4

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