Hypermethylation of Tumor Suppressor Genes BRCA1, p16 and 14-3-3s in Serum of Sporadic Breast Cancer Patients

2007 ◽  
Vol 30 (1-2) ◽  
pp. 14-19 ◽  
Author(s):  
Feng Jing ◽  
Jicai Zhang ◽  
Jianshu Tao ◽  
Youli Zhou ◽  
Lu Jun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Suppressor ◽  
Cancer Patients ◽  
Tumor Suppressor Genes ◽  
Sporadic Breast Cancer ◽  
Breast Cancer Patients ◽  
Suppressor Genes

scholarly journals Detection of aberrantly methylated tumor suppressor genes in breast cancer patients as a potential diagnostic biomarker

2021 ◽  
Author(s):  
Dejuan Yang ◽  
Yue Wu ◽  
Qin Xiang ◽  
Dishu Zhou ◽  
Zhu Qiu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Suppressor ◽  
Cancer Patients ◽  
Tumor Suppressor Genes ◽  
Hormone Receptors ◽  
Methylation Status ◽  
Cancer Tissue ◽  
Aberrant Methylation ◽  
Suppressor Genes ◽  
Significant Difference

Abstract Background: Aberrant methylation of tumor suppressor genes is a common feature of breast cancer. Identifying a panel of methylated genes that are sensitive and specific for breast cancer could help to diagnose and predict prognosis of breast cancer.Methods: We determined the methylation status of DACT1, PAX5, PLCD1, ZNF545 and TET1 in 32 benign controls, 237 cancer tissue samples and 33 paired plasma samples.Results: PAX5 and PLCD1 showed exceedingly high methylation rates with percentages of 69.2% and 54.9%, whereas the methylation percentage of DACT1, ZNF545 and TET1 were 33.8%, 28.7% and 18.2% in cancer samples, respectively. A better survival of patients with ZNF545 methylation (p = 0.0350) was detected. Correlation of promoter methylation and clinicopathological features in 32 individuals with benign disease and 237 cancer patients demonstrated that methylated status of DACT1 (p=0.012), PLCD1 (p=0.013), and ZNF545 (p=0.012) had significant difference in age, and the methylation of PAX5 (p=0.006) was correlated with absence of hormone receptors, which implied an adverse outcome. PAX5 and PLCD1 both had high sensitivity (69.20% and 54.85%, respectively) and high specificity (87.50% and 100.00%, respectively). Patients with methylation of PAX5 likely to have a higher risk of breast cancer (OR=15.726, 95% CI=5.323-46.463, p<0.001), and statistical analysis of public online database showed the similar results. Conclusion: PAX5, PLCD1, ZNF545 and TET1 may serve as new potential diagnostic and prognostic biomarkers for breast cancer.

scholarly journals Detection of a novel mutation in exon 20 of the BRCA1 gene

2013 ◽  
Vol 18 (4) ◽  
Author(s):  
Abhijit Chakraborty ◽  
Atul Katarkar ◽  
Keya Chaudhuri ◽  
Ashis Mukhopadhyay ◽  
Jayasri Basak
Keyword(s):  
Breast Cancer ◽  
Tumor Suppressor ◽  
Hereditary Breast Cancer ◽  
Tumor Suppressor Genes ◽  
Novel Mutation ◽  
Mutation Screening ◽  
Brct Domain ◽  
Globular Domain ◽  
Suppressor Genes ◽  
Exon 20

AbstractHereditary breast cancer constitutes 5–10% of all breast cancer cases. Inherited mutations in the BRCA1 and BRCA2 tumor-suppressor genes account for the majority of hereditary breast cancer cases. The BRCA1 C-terminal region (BRCT) has a functional duplicated globular domain, which helps with DNA damage repair and cell cycle checkpoint protein control. More than 100 distinct BRCA1 missense variants with structural and functional effects have been documented within the BRCT domain. Interpreting the results of mutation screening of tumor-suppressor genes that can have high-risk susceptibility mutations is increasingly important in clinical practice. This study includes a novel mutation, p.His1746 Pro (c.5237A>C), which was found in BRCA1 exon 20 of a breast cancer patient. In silico analysis suggests that this mutation could alter the stability and orientation of the BRCT domain and the differential binding of the BACH1 substrate.

scholarly journals Reversal of hypermethylation and reactivation of glutathione S-transferase pi 1 gene by curcumin in breast cancer cell line

Tumor Biology ◽  
2017 ◽  
Vol 39 (2) ◽  
pp. 101042831769225 ◽  
Author(s):  
Umesh Kumar ◽  
Ujjawal Sharma ◽  
Garima Rathi
Keyword(s):  
Breast Cancer ◽  
Tumor Suppressor ◽  
Breast Cancer Cell ◽  
Breast Cancer Cell Line ◽  
Tumor Suppressor Genes ◽  
Cancer Cell Line ◽  
Methylation Pattern ◽  
Glutathione S Transferase ◽  
Suppressor Genes ◽  
Mcf 7

One of the mechanisms for epigenetic silencing of tumor suppressor genes is hypermethylation of cytosine residue at CpG islands at their promoter region that contributes to malignant progression of tumor. Therefore, activation of tumor suppressor genes that have been silenced by promoter methylation is considered to be very attractive molecular target for cancer therapy. Epigenetic silencing of glutathione S-transferase pi 1, a tumor suppressor gene, is involved in various types of cancers including breast cancer. Epigenetic silencing of tumor suppressor genes can be reversed by several molecules including natural compounds such as polyphenols that can act as a hypomethylating agent. Curcumin has been found to specifically target various tumor suppressor genes and alter their expression. To check the effect of curcumin on the methylation pattern of glutathione S-transferase pi 1 gene in MCF-7 breast cancer cell line in dose-dependent manner. To check the reversal of methylation pattern of hypermethylated glutathione S-transferase pi 1, MCF-7 breast cancer cell line was treated with different concentrations of curcumin for different time periods. DNA and proteins of treated and untreated cell lines were isolated, and methylation status of the promoter region of glutathione S-transferase pi 1 was analyzed using methylation-specific polymerase chain reaction assay, and expression of this gene was analyzed by immunoblotting using specific antibodies against glutathione S-transferase pi 1. A very low and a nontoxic concentration (10 µM) of curcumin treatment was able to reverse the hypermethylation and led to reactivation of glutathione S-transferase pi 1 protein expression in MCF-7 cells after 72 h of treatment, although the IC50 value of curcumin was found to be at 20 µM. However, curcumin less than 3 µM of curcumin could not alter the promoter methylation pattern of glutathione S-transferase pi 1. Treatment of breast cancer MCF-7 cells with curcumin causes complete reversal of glutathione S-transferase pi 1 promoter hypermethylation and leads to re-expression of glutathione S-transferase pi 1, suggesting it to be an excellent nontoxic hypomethylating agent.

scholarly journals P4: CIRCULATING MIRNA PROFILES POINT TO DYSREGULATION IN TGFBETA/SMAD3 TUMOR SUPPRESSOR SIGNATURE IN BRCA POSITIVE BREAST CANCER PATIENTS

2016 ◽  
Vol 64 (3) ◽  
pp. 818.2-818
Author(s):  
I Shapira ◽  
T Bhuiya ◽  
S Arora ◽  
N Mukhi ◽  
S Datla ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Suppressor ◽  
Real Time ◽  
Cancer Patients ◽  
Survival Data ◽  
Real Time Pcr ◽  
Germ Line ◽  
Germline Mutations ◽  
Breast Cancer Patients ◽  
Mean Differences

Purpose of StudyOver 240,000 individuals are diagnosed with breast cancer (BrCa) of which 12,000 individuals carry BRCA germline mutations. MicroRNA dysregulation is common in malignancy and may correlate with germline mutations.Aims:1. Analyze microRNAs in patients with breast cancer with or without BRCA germ line mutations, with and without cancer.2. Identify molecular BRCA mutant patients to deduct reasons for accelerated malignancy.Methods UsedWe analyzed plasma miR expression from 94 br cancer patients (41 BRCA positive) relative to 24 normal controls. All samples were collected between 2010 and 2014 and survival data was known for all cancer patients. TaqMan Open Array panel was used to simultaneously run hundreds of microRNA assays in the Applied Biosystem Open array real time PCR. Using AB open array real time PCR, 756 miRNA species were detected. Two-sample t-test was used for all 2-sample comparison and ANOVA followed by Tukey HSD post-hoc test to compare the miRs mean differences. All tests were 2-tailed and results with a p<0.05 were considered statistically significant.Summary of ResultsBRCA+underexpressed hsa-mir-10a and hsa-mir-376c and over-expressed Hsa- mir- 326 and Hsa-mir-143 relative to BRCA-; p<0.05.Using Coremine data mining linking genes and diseases differentially expressed circulating miRs are linked to tumor suppressor TGFbeta/SMAD3.ConclusionsThe early onset of breast cancer in BRCA mutant patients may recapitulate the pro-oncogenic effects of TGF-β. The context dependent SMAD3 binding & tumor suppression TGF-β effects are abrogated in BRCA mutant patients. TGF-β/Smad3 tumor-suppressor signature suppresses local inflammation in the tumor microenvironment.

scholarly journals Targeting DNA methylation for treating triple-negative breast cancer

2019 ◽  
Vol 20 (16) ◽  
pp. 1151-1157 ◽  
Author(s):  
Jia Yu ◽  
Jacqueline Zayas ◽  
Bo Qin ◽  
Liewei Wang
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Tumor Suppressor ◽  
Triple Negative Breast Cancer ◽  
Targeted Therapies ◽  
Tumor Suppressor Genes ◽  
Dna Methyltransferase ◽  
Triple Negative ◽  
Suppressor Genes ◽  
Dna Methyltransferase Inhibitors

Triple-negative breast cancer (TNBC) accounts for 15–20% of all invasive breast cancers and tends to have aggressive histological features and poor clinical outcomes. Unlike, estrogen receptor- or HER2-positive diseases, TNBC patients currently lack the US FDA-approved targeted therapies. DNA methylation is a critical mechanism of epigenetic modification. It is well known that aberrant DNA methylation contributes to the malignant transformation of cells by silencing critical tumor suppressor genes. DNA methyltransferase inhibitors reactivate silenced tumor suppressor genes and result in tumor growth arrest, with therapeutic effects observed in patients with hematologic malignancies. The antitumor effect of these DNA methyltransferase inhibitors has also been explored in solid tumors, especially in TNBC that currently lacks targeted therapies.

scholarly journals Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) variants and breast cancer risk in Burkina Faso

2019 ◽  
Vol 10 (1) ◽  
pp. 175-183 ◽  
Author(s):  
Isabelle Touwendpoulimdé Kiendrebeogo ◽  
Abdou Azaque Zoure ◽  
Pegdwendé Abel Sorgho ◽  
Albert Théophane Yonli ◽  
Florencia Wendkuuni Djigma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Cancer Patients ◽  
Sporadic Breast Cancer ◽  
Disease Stage ◽  
Breast Cancer Patients ◽  
Glutathione S Transferase ◽  
Increased Risk ◽  
Increased Susceptibility

AbstractBackground and objectiveBreast cancer remains the most common cause of cancer mortality in women. The aim of this study was to investigate associations between genetic variability in GSTM1 and GSTT1 and susceptibility to breast cancer.MethodsGenomic DNA was extracted from blood samples for 80 cases of histologically diagnosed breast cancer and 100 control subjects. Genotyping analyses were performed by PCR-based methods. Associations between specific genotypes and the development of breast cancer were examined using logistic regression to calculate odds ratios [1] and 95% confidence intervals (95%CI).ResultsNo correlation was found between GSTM1-null and breast cancer (OR = 1.83; 95%CI 0.90-3.71; p = 0.10), while GSTT1-null (OR = 2.42; 95%CI 1.17-5.02; p= 0.01) was associated with increased breast cancer risk. The GSTM1/GSTT1 double null was not associated with an increased risk of developing breast cancer (OR = 2.52; 95%CI 0.75-8.45; p = 0.20). Furthermore, analysis found no association between GSTM1-null (OR =1.12; 95%CI 0.08-15.50; p = 1.00) or GSTT1-null (OR = 1.71; 95%CI 0.13-22.51; p = 1.00) and the disease stage of familial breast cancer patients or sporadic breast cancer patients (GSTM1 (OR = 0.40; 95%CI 0.12-1.32; p = 0.20) and GSTT1 (OR = 1.41; 95%CI 0.39-5.12; p = 0.75)). Also, body mass index (BMI) was not associated with increased or decreased breast cancer risk in either GSTM1-null (OR = 0.60; 95%CI 0.21-1.68; p = 0.44) or GSTT1-null (OR = 0.60; 95%CI 0.21-1.68; p =0.45).ConclusionOur results suggest that only GSTT1-null is associated with increased susceptibility to breast cancer development.

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