Article

Cancer epigenetics.

Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
CA A Cancer Journal for Clinicians (Impact Factor: 162.5). 10/2010; 60(6):376-92. DOI: 10.3322/caac.20085
Source: PubMed

ABSTRACT Epigenetics refers to stable alterations in gene expression with no underlying modifications in the genetic sequence and is best exemplified by differentiation, in which multiple cell types diverge physiologically despite a common genetic code. Interest in this area of science has grown over the past decades, especially since it was found to play a major role in physiologic phenomena such as embryogenesis, imprinting, and X chromosome inactivation, and in disease states such as cancer. The latter had been previously thought of as a disease with an exclusive genetic etiology. However, recent data have demonstrated that the complexity of human carcinogenesis cannot be accounted for by genetic alterations alone, but also involves epigenetic changes in processes such as DNA methylation, histone modifications, and microRNA expression. In turn, these molecular alterations lead to permanent changes in the expression of genes that regulate the neoplastic phenotype, such as cellular growth and invasiveness. Targeting epigenetic modifiers has been referred to as epigenetic therapy. The success of this approach in hematopoietic malignancies validates the importance of epigenetic alterations in cancer, not only at the therapeutic level but also with regard to prevention, diagnosis, risk stratification, and prognosis.

Download full-text

Full-text

Available from: Jean-Pierre Issa, Nov 24, 2014
0 Followers
 · 
117 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: MicroRNAs (miRNAs) are short non-coding RNAs of 20-24 nucleotides that play important roles in carcinogenesis. Accordingly, miRNAs control numerous cancer-relevant biological events such as cell proliferation, cell cycle control, metabolism and apoptosis. In this review, we summarize the current knowledge and concepts concerning the biogenesis of miRNAs, miRNA roles in cancer and their potential as biomarkers for cancer diagnosis and prognosis including the regulation of key cancer-related pathways, such as cell cycle control and miRNA dysregulation. Moreover, microRNA molecules are already receiving the attention of world researchers as therapeutic targets and agents. Therefore, in-depth knowledge of microRNAs has the potential not only to identify their roles in cancer, but also to exploit them as potential biomarkers for cancer diagnosis and identify therapeutic targets for new drug discovery.
    Asian Pacific journal of cancer prevention: APJCP 10/2014; 15(18):7489-97. DOI:10.7314/APJCP.2014.15.18.7489 · 2.51 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In cancer chemotherapy, one axiom, which has practically solidified into dogma, is that acquired resistance to antitumor agents or regimens, nearly inevitable in all patients with metastatic disease, remains unalterable and irreversible, rendering therapeutic rechallenge futile. However, the introduction of epigenetic therapies, including histone deacetylase inhibitors (HDACis) and DNA methyltransferase inhibitors (DNMTIs), provides oncologists, like computer programmers, with new techniques to “overwrite” the modifiable software pattern of gene expression in tumors and challenge the “one and done” treatment prescription. Taking the epigenetic code-as-software analogy a step further, if chemoresistance is the product of multiple nongenetic alterations, which develop and accumulate over time in response to treatment, then the possibility to hack or tweak the operating system and fall back on a “system restore” or “undo” feature, like the arrow icon in the Windows XP toolbar, reconfiguring the tumor to its baseline nonresistant state, holds tremendous promise for turning advanced, metastatic cancer from a fatal disease into a chronic, livable condition. This review aims 1) to explore the potential mechanisms by which a group of small molecule agents including HDACis (entinostat and vorinostat), DNMTIs (decitabine and 5-azacytidine), and redox modulators (RRx-001) may reprogram the tumor microenvironment from a refractory to a nonrefractory state, 2) highlight some recent findings, and 3) discuss whether the current “once burned forever spurned” paradigm in the treatment of metastatic disease should be revised to promote active resensitization attempts with formerly failed chemotherapies.
    Translational oncology 10/2014; 7(5):626–631. DOI:10.1016/j.tranon.2014.08.003 · 3.40 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Aberrant global DNA methylation is shown to increase cancer risk. LINE-1 has been proven a measure of global DNA methylation. The objectives of this study were to assess the association between LINE-1 methylation level and bladder cancer risk and to evaluate effect modification by environmental and genetic factors. Methods: Bisulphite-treated leukocyte DNA from 952 cases and 892 hospital controls was used to measure LINE-1 methylation level at four CpG sites by pyrosequencing. Logistic regression model was fitted to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Interactions between LINE-1 methylation levels and environmental and genetic factors were assessed. Results: The risk of bladder cancer followed a nonlinear association with LINE-1 methylation. Compared with subjects in the middle tertile, the adjusted OR for subjects in the lower and the higher tertiles were 1.26 (95% CI 0.99–1.60, P=0.06) and 1.33 (95% CI 1.05–1.69, P=0.02), respectively. This association significantly increased among individuals homozygous for the major allele of five single-nucleotide polymorphisms located in the phosphatidylethanolamine N-methyltransferase gene (corrected P-interaction<0.05). Conclusions: The findings from this large-scale study suggest that both low and high levels of global DNA methylation are associated with the risk of bladder cancer.
    British Journal of Cancer 03/2014; 110(8). DOI:10.1038/bjc.2014.67 · 4.82 Impact Factor