Epigenetic gene silencing in cancer: the DNA hypermethylome
Cancer Epigenetics Laboratory, Spanish National Cancer Centre (CNIO), Melchor Fernandez Almagro 3, 28029 Madrid, Spain
* To whom correspondence should be addressed at: Tel: +34 912246940; Fax: +34 912246923; Email: mesteller{at}cnio.es
Received January 9, 2007; Accepted January 19, 2007
Epigenetic gene inactivation in transformed cells involves many ‘belts of silencing’. One of the best-known lesions of the malignant cell is the transcriptional repression of tumor-suppressor genes by promoter CpG island hypermethylation. We are in the process of completing the molecular dissection of the entire epigenetic machinery involved in methylation-associated silencing, such as DNA methyltransferases, methyl-CpG binding domain proteins, histone deacetylases, histone methyltransferases, histone demethylases and Polycomb proteins. The first indications are also starting to emerge about how the combination of cellular selection and targeted pathways leads to abnormal DNA methylation. One thing is certain already, promoter CpG island hypermethylation of tumor-suppressor genes is a common hallmark of all human cancers. It affects all cellular pathways with a tumor-type specific profile, and in addition to classical tumor-suppressor and DNA repair genes, it includes genes involved in premature aging and microRNAs with growth inhibitory functions. The importance of hypermethylation events is already in evidence at the bedside of cancer patients in the form of cancer detection markers and chemotherapy predictors, and in the approval of epigenetic drugs for the treatment of hematological malignancies. In the very near future, the synergy of candidate gene approaches and large-scale epigenomic technologies, such as methyl-DIP, will yield the complete DNA hypermethylome of cancer cells.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Davidsson, H. Lilljebjorn, A. Andersson, S. Veerla, J. Heldrup, M. Behrendtz, T. Fioretos, and B. Johansson The DNA methylome of pediatric acute lymphoblastic leukemia Hum. Mol. Genet., November 1, 2009; 18(21): 4054 - 4065. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Benton, E. Crooke, and J. George Laminin-1 induces E-cadherin expression in 3-dimensional cultured breast cancer cells by inhibiting DNA methyltransferase 1 and reversing promoter methylation status FASEB J, November 1, 2009; 23(11): 3884 - 3895. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H.J. Hoeijmakers DNA Damage, Aging, and Cancer N. Engl. J. Med., October 8, 2009; 361(15): 1475 - 1485. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Fu, J. Zhang, F. Jin, J. Patchefsky, K.-H. Braunewell, and A. J. Klein-Szanto Promoter Regulation of the Visinin-like Subfamily of Neuronal Calcium Sensor Proteins by Nuclear Respiratory Factor-1 J. Biol. Chem., October 2, 2009; 284(40): 27577 - 27586. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J. Evison, R. A. Bilardi, F. C. K. Chiu, G. Pezzoni, D. R. Phillips, and S. M. Cutts CpG methylation potentiates pixantrone and doxorubicin-induced DNA damage and is a marker of drug sensitivity Nucleic Acids Res., October 1, 2009; 37(19): 6355 - 6370. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Phillips, L. D. Burgoon, and J. I. Goodman The Constitutive Active/Androstane Receptor Facilitates Unique Phenobarbital-Induced Expression Changes of Genes Involved in Key Pathways in Precancerous Liver and Liver Tumors Toxicol. Sci., August 1, 2009; 110(2): 319 - 333. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Okudela, T. Yazawa, T. Woo, M. Sakaeda, J. Ishii, H. Mitsui, H. Shimoyamada, H. Sato, M. Tajiri, N. Ogawa, et al. Down-Regulation of DUSP6 Expression in Lung Cancer: Its Mechanism and Potential Role in Carcinogenesis Am. J. Pathol., August 1, 2009; 175(2): 867 - 881. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Lee, J. Gaetz, B. Bugarija, C. J. Fernandes, G. E. Snyder, E. C. Bush, and B. T. Lahn Chromatin analysis of occluded genes Hum. Mol. Genet., July 15, 2009; 18(14): 2567 - 2574. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-H. Huang, S.-F. Huang, I-H. Chen, C.-T. Liao, H.-M. Wang, and L.-L. Hsieh Methylation of RASSF1A, RASSF2A, and HIN-1 Is Associated with Poor Outcome after Radiotherapy, but not Surgery, in Oral Squamous Cell Carcinoma Clin. Cancer Res., June 15, 2009; 15(12): 4174 - 4180. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K J Dudley, K Revill, R N Clayton, and W E Farrell Pituitary tumours: all silent on the epigenetics front J. Mol. Endocrinol., June 1, 2009; 42(6): 461 - 468. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Datta, K. Ghoshal, W. A. Denny, S. A. Gamage, D. G. Brooke, P. Phiasivongsa, S. Redkar, and S. T. Jacob A New Class of Quinoline-Based DNA Hypomethylating Agents Reactivates Tumor Suppressor Genes by Blocking DNA Methyltransferase 1 Activity and Inducing Its Degradation Cancer Res., May 15, 2009; 69(10): 4277 - 4285. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Gunduz, M. Gunduz, L. Beder, H. Nagatsuka, K. Fukushima, R. Sutcu, N. Delibas, N. Yamanaka, K. Shimizu, and N. Nagai Downregulation of TESTIN and Its Association With Cancer History and a Tendency Toward Poor Survival in Head and Neck Squamous Cell Carcinoma Arch Otolaryngol Head Neck Surg, March 1, 2009; 135(3): 254 - 260. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Ostrow, H. L. Park, M. O. Hoque, M. S. Kim, J. Liu, P. Argani, W. Westra, W. V. Criekinge, and D. Sidransky Pharmacologic Unmasking of Epigenetically Silenced Genes in Breast Cancer Clin. Cancer Res., February 15, 2009; 15(4): 1184 - 1191. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. Foley, J. M. Craig, R. Morley, C. J. Olsson, T. Dwyer, K. Smith, and R. Saffery Prospects for Epigenetic Epidemiology Am. J. Epidemiol., February 15, 2009; 169(4): 389 - 400. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. G. Guenther, L. N. Lawton, T. Rozovskaia, G. M. Frampton, S. S. Levine, T. L. Volkert, C. M. Croce, T. Nakamura, E. Canaani, and R. A. Young Aberrant chromatin at genes encoding stem cell regulators in human mixed-lineage leukemia Genes & Dev., December 15, 2008; 22(24): 3403 - 3408. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Hudder and R. F. Novak miRNAs: Effectors of Environmental Influences on Gene Expression and Disease Toxicol. Sci., June 1, 2008; 103(2): 228 - 240. [Abstract] [Full Text] [PDF]
|
|