CST6 promoter methylation in circulating cell-free DNA of breast cancer patients

Chimonidou, Maria; Tzitzira, Alexandra; Strati, Αreti; Sotiropoulou, Georgia; Sfikas, Costas; Malamos, Nikos; Georgoulias, Vasilis; Lianidou, Evi

doi:10.1016/j.clinbiochem.2012.09.015

Cited by 71 publications

(53 citation statements)

References 37 publications

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“…After excluding non-eligible articles (see Fig. 1a and Additional file 1: Supplementary materials), 45 articles could be included in this review, including 26 articles used DNA isolated from whole blood [14–21, 24–41], two articles used DNA isolated from both whole blood and plasma [42, 43], six articles used DNA isolated from plasma [44–49], and 11 articles used DNA isolated from serum [50–60] (Table 1). For the studies that used serum or plasma as DNA source, four of them used two centrifugation steps to get serum or plasma [42, 45, 47, 48] and the rest used one centrifugation step or sample processing procedures are not available (Table 1).…”

Section: Resultsmentioning

confidence: 99%

Blood-based DNA methylation as biomarker for breast cancer: a systematic review

et al. 2016

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Multiple studies have investigated global DNA methylation profiles and gene-specific DNA methylation in blood-based DNA to develop powerful screening markers for cancer. This systematic review summarizes the current evidence on methylation studies that investigated methylation level of blood-derived DNA of breast cancer (BC) patients in comparison to healthy controls by conducting a systematic literature review in PubMed and Web of Science. Essential results, such as methylation levels of BC cases and healthy controls, p values, and odds ratios, were extracted from these studies by two investigators independently. Overall, 45 publications met the inclusion criteria for this review. DNA from whole blood, as well as cell-free DNA (cfDNA) from serum or plasma, was used in these studies. The most common method used for measuring global DNA methylation was the investigation of repetitive elements as surrogates and the application of array-based genome-wide methylation analysis. For measuring gene-specific methylation level, methylation-specific PCR and pyrosequencing were the most frequently used methods. Epigenome-wide blood DNA hypomethylation in BC patients were reported in several studies; however, the evidence is still not conclusive. The most frequently investigated gene in whole blood was BRCA1, which was found more frequently methylated in patients compared to controls. RASSF1A was the most widely investigated gene in cfDNA of serum or plasma, which was also found more frequently methylated in patients compared to controls. Several of the eligible studies reported the associations of global hypomethylation and increased BC risk. Studies investigated associations between gene-specific methylation and BC risk, while got heterogeneous results. But two studies reported that hypermethylation of ATM gene was associated with increased BC risk, which suggest the potential use of this gene for BC risk stratification. Overall, our review suggests the possibility of using blood-based DNA methylation marker as promising marker for BC risk stratification, as several studies found associations between certain methylation level in blood and BC risk. However, so far, the evidence is still quite limited. Optimal markers are yet to be developed and promising results needed to be validated in prospective study cohorts and tested in large screening populations.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-016-0282-6) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Blood-based DNA methylation as biomarker for breast cancer: a systematic review

et al. 2016

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“…Furthermore, recent publications have shown the prognostic potential of methylated DNA, readily detected in serum samples from patients with breast cancer (36,37). The detection of methylated DNA as a biomarker of disease has several advantages over protein-based assays as defined regions of cancer-specific hypermethylated-DNA can be readily amplified from samples collected noninvasively using PCR-based technology (38).…”

Section: Discussionmentioning

confidence: 99%

BCL-2 Hypermethylation Is a Potential Biomarker of Sensitivity to Antimitotic Chemotherapy in Endocrine-Resistant Breast Cancer

Stone

Cowley

Valdés-Mora

et al. 2013

Molecular Cancer Therapeutics

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Overexpression of the antiapoptotic factor BCL-2 is a frequent feature of malignant disease and is commonly associated with poor prognosis and resistance to conventional chemotherapy. In breast cancer, however, high BCL-2 expression is associated with favorable prognosis, estrogen receptor (ER) positivity, and low tumor grade, whereas low expression is included in several molecular signatures associated with resistance to endocrine therapy. In the present study, we correlate BCL-2 expression and DNA methylation profiles in human breast cancer and in multiple cell models of acquired endocrine resistance to determine whether BCL-2 hypermethylation could provide a useful biomarker of response to cytotoxic therapy. In human disease, diminished expression of BCL-2 was associated with hypermethylation of the second exon, in a region that overlapped a CpG island and an ER-binding site. Hypermethylation of this region, which occurred in 10% of primary tumors, provided a stronger predictor of patient survival (P ¼ 0.019) when compared with gene expression (n ¼ 522). In multiple cell models of acquired endocrine resistance, BCL-2 expression was significantly reduced in parallel with increased DNA methylation of the exon 2 region. The reduction of BCL-2 expression in endocrine-resistant cells lowered their apoptotic threshold to antimitotic agents: nocodazole, paclitaxel, and the PLK1 inhibitor BI2536. This phenomenon could be reversed with ectopic expression of BCL-2, and rescued with the BCL-2 inhibitor ABT-737. Collectively, these data imply that BCL-2 hypermethylation provides a robust biomarker of response to current and next-generation cytotoxic agents in endocrine-resistant breast cancer, which may prove beneficial in directing therapeutic strategy for patients with nonresectable, metastatic disease. Mol Cancer Ther; 12(9); 1874-85. Ó2013 AACR.

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“…In addition to multi-gene expression assays, DNA methylation signatures are being assessed as potential molecular biomarkers of cancer 8 . A number of studies have documented aberrant methylation events in breast carcinogenesis and identified specific DNA methylation biomarkers that have significant diagnostic and prognostic potential [9][10][11][12] . Several studies have also identified DNA methylation signatures that can distinguish between breast cancer subtypes [13][14][15][16] , and others that may be predictive of treatment response [17][18][19] .…”

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Methylome sequencing in triple-negative breast cancer reveals distinct methylation clusters with prognostic value

et al. 2015

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Epigenetic alterations in the cancer methylome are common in breast cancer and provide novel options for tumour stratification. Here, we perform whole-genome methylation capture sequencing on small amounts of DNA isolated from formalin-fixed, paraffin-embedded tissue from triple-negative breast cancer (TNBC) and matched normal samples. We identify differentially methylated regions (DMRs) enriched with promoters associated with transcription factor binding sites and DNA hypersensitive sites. Importantly, we stratify TNBCs into three distinct methylation clusters associated with better or worse prognosis and identify 17 DMRs that show a strong association with overall survival, including DMRs located in the Wilms tumour 1 (WT1) gene, bi-directional-promoter and antisense WT1-AS. Our data reveal that coordinated hypermethylation can occur in oestrogen receptor-negative disease, and that characterizing the epigenetic framework provides a potential signature to stratify TNBCs. Together, our findings demonstrate the feasibility of profiling the cancer methylome with limited archival tissue to identify regulatory regions associated with cancer.

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CST6 promoter methylation in circulating cell-free DNA of breast cancer patients

Cited by 71 publications

References 37 publications

Blood-based DNA methylation as biomarker for breast cancer: a systematic review

Blood-based DNA methylation as biomarker for breast cancer: a systematic review

BCL-2 Hypermethylation Is a Potential Biomarker of Sensitivity to Antimitotic Chemotherapy in Endocrine-Resistant Breast Cancer

Methylome sequencing in triple-negative breast cancer reveals distinct methylation clusters with prognostic value

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