Epigenetics and cancer treatment

Kristensen, Lasse Sommer; Nielsen, Henning Overgaard; Hansen, Lise Lotte

doi:10.1016/j.ejphar.2009.10.011

Cited by 204 publications

(161 citation statements)

References 159 publications

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Section: Discussionmentioning

confidence: 99%

“…[44][45][46] DNMT and histone deacetylases (HDAC) have become the primary targets for the epigenetic regulation of cancer. 45,46 If DNMT and HDAC inhibitors act by reactivating TSGs, DNA methylation status may be used as a biomarker to predict response to treatment with these drugs. 45 As basal-like subtype of breast cancer or breast cancer with stem cell phenotype was found to be less methylated in the genes involved in breast cancer progression, the agents that modulate epigenetic changes may be less effective in those cases.…”

Section: Discussionmentioning

confidence: 99%

“…45,46 If DNMT and HDAC inhibitors act by reactivating TSGs, DNA methylation status may be used as a biomarker to predict response to treatment with these drugs. 45 As basal-like subtype of breast cancer or breast cancer with stem cell phenotype was found to be less methylated in the genes involved in breast cancer progression, the agents that modulate epigenetic changes may be less effective in those cases. Conversely, as breast cancers with luminal-HER2 subtype or more differentiated cell phenotype show high level of promoter CpG islands methylation, they may be good targets for epigenetic therapy.…”

Section: Discussionmentioning

confidence: 99%

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Distinct patterns of promoter CpG island methylation of breast cancer subtypes are associated with stem cell phenotypes

et al. 2012

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Although DNA methylation profiles in breast cancer have been connected to breast cancer molecular subtype, there have been no studies of the association of DNA methylation with stem cell phenotype. This study was designed to evaluate the promoter CpG island methylation of 15 genes in relation to breast cancer subtype, and to investigate whether the patterns of CpG island methylation in each subtype are associated with their cancer stem cell phenotype represented by CD44 þ /CD24À and ALDH1 expression. We performed MethyLight analysis of the methylation status of 15 promoter CpG island loci involved in breast cancer progression (APC, DLEC1, GRIN2B, GSTP1, HOXA1, HOXA10, IGF2, MT1G, RARB, RASSF1A, RUNX3, SCGB3A1, SFRP1, SFRP4, and TMEFF2) and determined cancer stem cell phenotype by CD44/CD24 and ALDH1 immunohistochemistry in 36 luminal A, 33 luminal B, 30 luminal-HER2, 40 HER2 enriched, and 40 basal-like subtypes of breast cancer. The number of CpG island loci methylated differed significantly between subtypes, and was highest in the luminal-HER2 subtype and lowest in the basal-like subtype. Methylation frequencies and levels in 12 of the 15 genes differed significantly between subtypes, and the basal-like subtype had significantly lower methylation frequencies and levels in nine of the genes than the other subtypes. CD44 þ /CD24À and ALDH1 þ putative stem cell populations were most enriched in the basal-like subtype. Methylation of promoter CpG islands was significantly lower in CD44 þ /CD24-cell ( þ ) tumors than in CD44 þ /CD24-cell (À) tumors, even within the basallike subtype. ALDH1 ( þ ) tumors were also less methylated than ALDH1 (À) tumors. Our findings showed that promoter CpG island methylation was different in relation to breast cancer subtype and stem cell phenotype of tumor, suggesting that breast cancers have distinct patterns of CpG island methylation according to molecular subtypes and these are associated with different stem cell phenotypes of the tumor.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Distinct patterns of promoter CpG island methylation of breast cancer subtypes are associated with stem cell phenotypes

et al. 2012

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“…Though many HDAC inhibitors are at various stages of clinical testing for cancer therapy, 6) the roles of HDACs in carcinogenesis remain unclear. In this study, we cloned rat Hdac9 cDNA and showed that Hdac9 was expressed during hepatocarcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…3,4) Several HDAC inhibitors are currently in clinical trials for some cancers. 5,6) * To whom correspondence should be addressed: Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan. Tel.…”

Section: Introductionmentioning

confidence: 99%

Promotion of Anchorage-independent Growth by Cytoplasmic and Nuclear Histone Deacetylase 9

Yura

Hashizume

Suzuki

et al. 2010

JOURNAL OF HEALTH SCIENCE

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Genetic mutation is a trigger for the generation of malignant cells and an aberrant epigenetic status contributes to the maintenance of mutations and proliferation of mutated cells. Along with DNA methylation, histone modifications such as acetylation and methylation are significant to biological processes. Histone deacetylases (HDACs) are important epigenetic regulators of chromatin modifications and gene expression. Though several HDAC inhibitors are currently being tested in clinical trials, the roles of HDACs in malignant transformation remain unknown. Here, we showed that the expression of two forms of Hdac9, a full-length version (Hdac9FL) and a splicing variant lacking exon 7 (Hdac9∆7), both class IIa HDACs, was up-regulated during chemically induced hepatocarcinogenesis. In addition, we found that HDAC9FL and HDAC9∆7 are located in the nucleus and cytoplasm, respectively. We also found their nuclear localization and nuclear export signals to be encoded in exon 7 and exon 25, respectively. Though the two isoforms could not transform mouse NIH-3T3 fibroblasts, they promoted tumor cell anchorageindependent growth on soft agarose. The HDAC9 variants do not seem to cause cell transformation, but cytoplasmic and nuclear HDAC9 may contribute to the survival of malignant cells in the early stages of hepatocarcinogenesis.

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Analysis of Epigenetic Modifications of DNA in Human Cells

2013

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Epigenetics, the study of somatically heritable changes in gene expression not related to changes in the DNA sequence, is a rapidly expanding research field that plays important roles in healthy as well as in diseased cells. DNA methylation and hydroxymethylation are epigenetic modifications found in human cells, which are deeply implicated in normal cellular processes as well as in several major human diseases. Here, a range of different methods for the analyses of DNA methylation and hydroxymethylation at locus-specific and genome-wide scales is described.

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Epigenetics and cancer treatment

Cited by 204 publications

References 159 publications

Distinct patterns of promoter CpG island methylation of breast cancer subtypes are associated with stem cell phenotypes

Distinct patterns of promoter CpG island methylation of breast cancer subtypes are associated with stem cell phenotypes

Promotion of Anchorage-independent Growth by Cytoplasmic and Nuclear Histone Deacetylase 9

Analysis of Epigenetic Modifications of DNA in Human Cells

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