DNA methylation and breast carcinogenesis

Widschwendter, Martin; Jones, Peter A.

doi:10.1038/sj.onc.1205606

Cited by 416 publications

(363 citation statements)

References 195 publications

(178 reference statements)

Supporting

Mentioning

354

Contrasting

Unclassified

Order By: Relevance

“…These genes had been reported to be frequently methylated in breast cancer (Esteller et al, 2001;Jones and Baylin, 2002;Widschwendter and Jones, 2002). CirDNA isolated from the plasma of 10 healthy women were found to be negative for methylation forms of all three genes.…”

Section: Resultsmentioning

confidence: 90%

“…Changes in the status of DNA methylation represent one of the most common molecular alterations in human neoplasia (Egger et al, 2004), including breast cancer (Widschwendter and Jones, 2002). These epigenetic alterations induce neoplastic process by transcriptional silencing of tumour suppressor gene expression and are responsible for initial steps of induction of tumour cell proliferation (Jones and Baylin, 2002).…”

mentioning

confidence: 99%

“…Therefore, analysis of gene methylation patterns in tissues could be of profound significance in the early detection of cancer (Esteller et al, 2001). Expression of more than 40 genes was found to be lost in breast cancer because of promoter hypermethylation (Jones and Baylin, 2002;Widschwendter and Jones, 2002), including RASS-F1A, RARb2, HIC-1 genes. However, the methylated markers are detected with twice lower frequency in plasma samples compared with the frequency of their finding in the tissues of cancer patient (Shao and Nguyen, 2002;Anker P et al, 2003).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Cell-free and cell-bound circulating DNA in breast tumours: DNA quantification and analysis of tumour-related gene methylation

et al. 2006

View full text Add to dashboard Cite

Tumour development is characterised by the increased circulating DNA (cirDNA) concentration and by tumour-related changes in blood plasma DNA. Concentration of cirDNA and methylation of RARb2, RASSF1A and HIC-1 gene promoters were investigated in cell-free and cell-surface-bound fractions from healthy donors, patients with breast cancer, and patients with breast fibroadenoma. Tumour development was shown to lead to significant changes in the distribution of cirDNA between cell-free and cell-surfacebound fractions. Analysis of RARb2 and RASSF1A methylation in the total cirDNA provides 95% diagnostic coverage in breast cancer patients, 60% in patients with benign lesions, and is without false-positive results in healthy women. Results of the study indicate that methylation-specific PCR of RARb2 and RASSF1A genes based on the total cirDNA combined with the quantitative analysis of cirDNA distribution between cell-bound and cell-free fractions in blood provide the sensitive and accurate detection and discrimination of malignant and benign breast tumours.

show abstract

Section: Resultsmentioning

confidence: 90%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Cell-free and cell-bound circulating DNA in breast tumours: DNA quantification and analysis of tumour-related gene methylation

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Resistance to endocrine therapies is a major issue in recurrent ER+ HBC patients (De Marchi et al ., 2016). Several mechanisms have been connected to endocrine resistance, such as mutation in the ligand‐binding domain of the ER (Toy et al ., 2013), enhanced growth factor signaling, altered DNA methylation of specific genes (Graff et al ., 1995; Widschwendter and Jones, 2002), or the dysregulation of metabolic pathways (Wang et al ., 2016). In our study, we discovered a novel mechanism demonstrating that Tam decreases Brf1 expression and Pol III gene transcription (Fig.…”

Section: Discussionmentioning

confidence: 99%

Role of Brf1 interaction with ERα, and significance of its overexpression, in human breast cancer

Zeng

Shi

et al. 2017

Molecular Oncology

View full text Add to dashboard Cite

TFIIB‐related factor 1 (Brf1) modulates the transcription of RNA Pol III genes (polymerase‐dependent genes). Upregulation of Pol III genes enhances tRNA and 5S RNA production and increases the translational capacity of cells to promote cell transformation and tumor development. However, the significance of Brf1 overexpression in human breast cancer (HBC) remains to be investigated. Here, we investigate whether Brf1 expression is increased in the samples of HBC, and we explore its molecular mechanism and the significance of Brf1 expression in HBC. Two hundred and eighteen samples of HBC were collected to determine Brf1 expression by cytological and molecular biological approaches. We utilized colocalization, coimmunoprecipitation, and chromatin immunoprecipitation methods to explore the interaction of Brf1 with estrogen receptor alpha (ERα). We determined how Brf1 and ERα modulate Pol III genes. The results indicated that Brf1 is overexpressed in most cases of HBC, which is associated with an ER‐positive status. The survival period of the cases with high Brf1 expression is significantly longer than those with low levels of Brf1 after hormone treatment. ERα mediates Brf1 expression. Brf1 and ERα are colocalized in the nucleus. These results indicate an interaction between Brf1 and ERα, which synergistically regulates the transcription of Pol III genes. Inhibition of ERα by its siRNA or tamoxifen reduces cellular levels of Brf1 and Pol III gene expression and decreases the rate of colony formation of breast cancer cells. Together, these studies demonstrate that Brf1 is a good biomarker for the diagnosis and prognosis of HBC. This interaction of Brf1 with ERα and Brf1 itself are potential therapeutic targets for this disease.

show abstract

“…4,5 As in other types of human cancer, breast cancer development involves the accumulation of both genetic alterations such as amplification of oncogenes and mutation or loss of tumor suppressor genes (TSGs) and epigenetic alterations such as DNA methylation and histone modification. 6,7 Cancer-related DNA methylation involves genomic DNA hypomethylation associated with chromosomal instability and hypermethylation of promoter CpG islands, the latter representing an alternative mechanism for inactivating TSGs, resulting in their transcriptional silencing. 8,9 In breast cancer, promoter CpG island hypermethylation has been described for genes involved in all aspects of cellular function.…”

mentioning

confidence: 99%

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

et al. 2012

View full text Add to dashboard Cite

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.

show abstract

DNA methylation and breast carcinogenesis

Cited by 416 publications

References 195 publications

Cell-free and cell-bound circulating DNA in breast tumours: DNA quantification and analysis of tumour-related gene methylation

Cell-free and cell-bound circulating DNA in breast tumours: DNA quantification and analysis of tumour-related gene methylation

Role of Brf1 interaction with ERα, and significance of its overexpression, in human breast cancer

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

Contact Info

Product

Resources

About