DNA methylation profile of triple negative breast cancer specific genes
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE78758 | GEO | 2017/02/10
SECONDARY ACCESSION(S): PRJNA313436
REPOSITORIES: GEO
Similar Datasets
Project description:Purpose Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype with no targeted treatment available. Our previous study identified 38 TNBC-specific genes with altered expression in tumour samples compared to normal samples. This study aimed to identify whether DNA methylation contributed to these gene expression changes in the same breast cancer cohort. Additionally, we aimed to identify a whole genome methylation profile that contributes to the progression from primary breast tumour to lymph node metastasis. Methods We used the DNA of 23 primary TNBC samples, 12 matched lymph node metastases, and 11 matched normal adjacent tissues to perform 450K Illumina methylation arrays. The results were validated in an independent cohort of 70 primary TNBC samples. Results The gene expression of 16/38 TNBC-specific genes was associated with significantly altered methylation. Furthermore, altered methylation of 18 genes associated with lymph node metastasis was identified and validated in an independent cohort. Additionally, novel methylation changes between primary tumours and lymph node metastases, as well as those associated with survival were identified. Conclusion This study has shown that DNA methylation plays an important role in altered gene expression patterns of TNBC-specific genes and is the first study to perform whole genome DNA methylation analysis that includes matched lymph node metastases in this breast cancer subtype. This novel insight into the progression of TNBC to secondary cancers may provide potential prognostic indicators for this hard-to-treat breast cancer subtype. Validation cohort (70 IDC TNBC samples)
2017-02-10 | GSE78754 | GEO
Project description:Purpose Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype with no targeted treatment available. Our previous study identified 38 TNBC-specific genes with altered expression in tumour samples compared to normal samples. This study aimed to identify whether DNA methylation contributed to these gene expression changes in the same breast cancer cohort. Additionally, we aimed to identify a whole genome methylation profile that contributes to the progression from primary breast tumour to lymph node metastasis. Methods We used the DNA of 23 primary TNBC samples, 12 matched lymph node metastases, and 11 matched normal adjacent tissues to perform 450K Illumina methylation arrays. The results were validated in an independent cohort of 70 primary TNBC samples. Results The gene expression of 16/38 TNBC-specific genes was associated with significantly altered methylation. Furthermore, altered methylation of 18 genes associated with lymph node metastasis was identified and validated in an independent cohort. Additionally, novel methylation changes between primary tumours and lymph node metastases, as well as those associated with survival were identified. Conclusion This study has shown that DNA methylation plays an important role in altered gene expression patterns of TNBC-specific genes and is the first study to perform whole genome DNA methylation analysis that includes matched lymph node metastases in this breast cancer subtype. This novel insight into the progression of TNBC to secondary cancers may provide potential prognostic indicators for this hard-to-treat breast cancer subtype. study cohort
2017-02-10 | GSE78751 | GEO
Project description:This part of the study was used to validate our findings comparing the DNA methylation in lymph node metastasis to that in normal tissue. We compared our findings (comparing LN versus NAT) with MBDcap sequencing data provided by Dr. Clare Stirzaker and Prof. Susan Clark from the Garvan Institute Sydney. This analysis provides regional DNA methylation information therefore a strict validation with our CpG-specific analysis was not possible. The regions that were analysed using the MBDcap data included our genes of interest (83 genes that are associated with LN metastasis, identified in 16) starting 2kb upstream of the first transcription start site (TSS) to the 3’ end of the genes. These regions are broken up into 1kb tiles. Methylation differences between LN and NAT samples were assessed using a Student’s t-test (using the R base package) (p<0.05).
2017-02-10 | GSE79163 | GEO
Project description:Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype with no targeted treatment available. Our previous study identified 38 TNBC-specific genes with altered expression comparing tumour to normal samples. This study aimed to establish whether DNA methylation contributed to these expression changes in the same cohort as well as disease progression from primary breast tumour to lymph node metastasis associated with changes in the epigenome. We obtained DNA from 23 primary TNBC samples, 12 matched lymph node metastases, and 11 matched normal adjacent tissues and assayed for differential methylation profiles using Illumina HumanMethylation450 BeadChips. The results were validated in an independent cohort of 70 primary TNBC samples. The expression of 16/38 TNBC-specific genes was associated with alteration in DNA methylation. Novel methylation changes between primary tumours and lymph node metastases, as well as those associated with survival were identified. Altered methylation of 18 genes associated with lymph node metastasis were identified and validated. This study reveals the important role DNA methylation plays in altered gene expression of TNBC-specific genes and lymph node metastases. The novel insights into progression of TNBC to secondary disease may provide potential prognostic indicators for this hard-to-treat breast cancer subtype.
| S-EPMC5037364 | biostudies-literature
Project description:DNA methylation profile of triple negative breast cancer specific genes
| PRJNA313436 | ENA
Project description:Here, we present a next-generation sequencing (NGS) methylation-based blood test called methylation DETEction of Circulating Tumour DNA (mDETECT) designed for the optimal detection and monitoring of metastatic triple-negative breast cancer (TNBC). Based on a highly multiplexed targeted sequencing approach, this assay incorporates features that offer superior performance and included 53 amplicons from 47 regions. Analysis of a previously characterised cohort of women with metastatic TNBC with limited quantities of plasma (<2 ml) produced an AUC of 0.92 for detection of a tumour with a sensitivity of 76% for a specificity of 100%. mDETECTTNBC was quantitative and showed superior performance to an NGS TP53 mutation-based test carried out on the same patients and to the conventional CA15-3 biomarker. mDETECT also functioned well in serum samples from metastatic TNBC patients where it produced an AUC of 0.97 for detection of a tumour with a sensitivity of 93% for a specificity of 100%. An assay for BRCA1 promoter methylation was also incorporated into the mDETECT assay and functioned well but its clinical significance is currently unclear. Clonal Hematopoiesis of Indeterminate Potential was investigated as a source of background in control subjects but was not seen to be significant, though a link to adiposity may be relevant. The mDETECTTNBC assay is a liquid biopsy able to quantitatively detect all TNBC cancers and has the potential to improve the management of patients with this disease.
| S-EPMC8209161 | biostudies-literature
Project description:All-trans retinoic acid (atRA) regulates gene expression and is used to treat acute promyelocytic leukemia. Attempts to use atRA for breast cancer treatment without a stratification strategy have resulted in limited overall effectiveness. To identify biomarkers for the treatment of triple-negative breast cancer (TNBC) with atRA, we characterized the effects of atRA on the tumor growth of 13 TNBC cell lines. This resulted in a range of tumor growth effects that was not predictable based on the levels of retinoid signaling molecules and transcriptional responses that were mostly independent of retinoic acid response elements. Given the importance of DNA methylation in regulating gene expression, we hypothesized that differential DNA methylation could predict the response of TNBCs to atRA. We identified over 1400 CpG sites that were differentially methylated between atRA resistant and sensitive cell lines. These CpG sites predicted the response of four TNBC patient-derived xenografts to atRA treatment and we utilized these xenografts to refine the profile to 6 CpGs. We identify as many as 17% of TNBC patients who could benefit from atRA treatment. These data illustrate that differential DNA methylation of specific sites may predict the response of patient tumors to atRA treatment.
2018-10-22 | GSE117926 | GEO
Project description:We lack tools to risk-stratify triple-negative breast cancer (TNBC). Our goal was to develop molecular tools to predict disease recurrence. Methylation array analysis was performed on 110 samples treated by locoregional therapy obtained from institutional cohorts. Discovered marker sets were then tested by Kaplan-Meier analyses in a prospectively collected TNBC cohort of 49 samples from the no-chemotherapy arms of IBCSG trials VIII and IX, and by logistic regression in a chemotherapy-treated cohort of 121 TNBCs from combined IBCSG trials and institutional repositories. High methylation was associated with shorter recurrence-free interval in the no-chemotherapy arm of the IBCSG studies, as well as in the chemotherapy-treated patients within the combined institutional and IBCSG chemotherapy cohorts (100 marker panel, p = 0.002; 30 marker panel, p = 0.05). Chromosome 19 sites were enriched among these loci. In conclusion, our hypermethylation signatures identify increased recurrence risk independent of whether patients receive chemotherapy.
| S-EPMC6994477 | biostudies-literature
Project description:We lack tools to risk-stratify triple-negative breast cancer (TNBC). Our goal was to develop molecular tools to predict disease recurrence. Methylation array analysis was performed on 110 samples treated by locoregional therapy obtained from Institutional cohorts. Discovered marker sets were then tested by Kaplan Meier analyses in a prospectively collected TNBC cohort of 49 samples from the no chemotherapy arms of IBCSG trials VIII and IX, and by logistic regression in a chemotherapy-treated cohort of 121 TNBCs from combined IBCSG trials and Institutional repositories. High methylation was associated with shorter recurrence-free interval in the no chemotherapy arm of the IBCSG studies, as well as in the chemotherapy-treated patients within the combined Institutional and IBCSG chemotherapy cohorts (100 marker panel, P=0.002; 30 marker panel, P=0.05). Chromosome 19 sites were enriched among these loci. In conclusion, our hypermethylation signatures identify increased recurrence risk independent of whether patients receive chemotherapy.
2019-12-05 | GSE141441 | GEO
Project description:Analysis of DNA methylation changes after prolonged exposure of triple-negative breast cancer cell lines to low doses of Panobinostat (LBH589), a pan-histone deacetylase inhibitor.
2017-02-14 | GSE92909 | GEO