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Concordance of DNA methylation profiles between breast core biopsy and surgical excision specimens containing ductal carcinoma in situ (DCIS)

ABSTRACT: Whether DNA methylation in ductal carcinoma in situ (DCIS), measured in core biopsy and surgical specimens are similar, remains unclear. Here, we compared genome-scale DNA methylation measured in matched core biopsy and surgical specimens from DCIS, including specific DNA methylation biomarkers of subsequent invasive cancer. This study aims to compare genome-scale DNA methylation between core biopsies (in this GEO accession) and surgical specimens (previously published in GSE66313; see Overall Design below). Within-subject variability in DNA methylation was significantly lower than between-subject variability (all P < 2.20E-16). In 641 CpGs whose methylation was related with increased hazard of invasive breast cancer, lower within-subject than between-subject variability was observed in 92.3% of the study participants (P < 0.05). Between patient-matched core biopsy and surgical specimens, < 0.6% of CpGs measured had changes in median DNA methylation > 15%, and a pathway analysis of these CpGs indicated enrichment for genes related with wound healing. Our results indicate that DNA methylation measured in core biopsies are representative of the matched surgical specimens and suggest that DCIS biomarkers measured in core biopsies can inform clinical decision-making.

ORGANISM(S): Homo sapiens

PROVIDER: GSE100503 | GEO | 2018/02/15

REPOSITORIES: GEO

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Homo sapiens

Project description:Concordance of DNA methylation profiles between breast core biopsy and surgical excision specimens containing ductal carcinoma in situ (DCIS)

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Breast cancer risk factors are associated with DNA methylation in non-diseased breast tissue independent of cell type

Project description:The underlying biology through which established breast cancer risk factors contribute to disease risk is not well characterized. One key risk factor for breast cancer is age, and age-related DNA methylation alterations may contribute to increased risk of disease. Here we assessed normal breast tissues and tested the relation of DNA methylation with known breast cancer risk factors. Cancer-free women donated breast tissue biopsy specimens through the Susan G. Komen Foundation and provided detailed risk factor data (n=100). Bisulfite modified DNA was profiled for DNA methylation genome-wide using the Infinium 450K DNA methylation array. We tested the relation of known breast cancer risk factors such as age, BMI, parity, and family history of disease with DNA methylation adjusted for variation in cell type proportions using a novel cellular mixture deconvolution algorithm. We identified 787 CpGs that exhibited significant (FDR adjusted, q-value < 0.01) differential DNA methylation associated with subject age, but not with other breast cancer risk factors. We observed an enrichment among the risk factor-related CpGs for Polycomb group target genes (Fisher’s Exact test, P = 1.74E-06), and breast myoepithelial cell enhancer regions (H3K4me1; Fisher’s Exact test, P = 7.1E-20). We validated our risk factor-related findings in two independent populations of normal breast tissue (n=18 and n=97). In addition, age-related CpGs were further deregulated in both pre-invasive (DCIS, n=40) and invasive breast cancers (TCGA, n=731). Overall, our results suggest that the breast cancer risk factor age contributes to epigenetic dysregulation in normal breast tissue that exhibit progressive changes in cancer.

2017-06-20 | GSE88883 | GEO

Genome wide DNA methylation profile in expressed prostatic secretions of normal and, benign and malignant prostatic lesions of diseased individuals

Project description:Genome wide DNA methylation profiling was done on expressed prostatic secretions (EPS) of normal individuals and dry-core needle biopsy samples of benign and malignant (Primary tumor) prostatic lesions. The Illumina Infinium 850k Infinium MethylationEPIC v 1.0 was used to obtain DNA methylation profiles across approximately 850,000 CpGs in EPS and prostatic lesion biopsy samples. Samples included 4 EPS of normal individuals, and 8 biopsy tissues of benign, and malignant lesions each of patient individuals.

2024-09-02 | GSE241670 | GEO

DNA methylation in ductal carcinoma in situ related with future development of invasive breast cancer

Project description:Ductal carcinoma in situ (DCIS) is a heterogeneous, pre-invasive lesion associated with an increased risk for future invasive ductal carcinoma. However, accurate risk stratification for development of invasive disease and appropriate treatment decisions remain clinical challenges. DNA methylation alterations are recognized to be early events in the progression of cancer and represent emerging molecular markers that may predict invasive recurrence more accurately than traditional measures of DCIS prognosis. We measured DNA methylation of DCIS (n=40) and adjacent normal (n=15) tissues using the Illumina HumanMethylation450 array. We identified locus-specific methylation differences between DCIS and matched adjacent-normal tissue (95,609 CpGs, Q < 0.05). Among 40 DCIS cases 13 later developed invasive disease and we identified 641 CpG sites that exhibited differential DNA methylation (P < 0.01 and medianúΔβú > 0.1) in these cases compared with age-matched subjects without invasive disease over a similar follow up period. The set of differentially methylated CpG loci associated with disease progression was enriched in homeobox-containing genes (P = 1.3E-9) and genes involved with limb morphogenesis (P = 1.0E-05). In an independent cohort, a subset of genes with progression-related differential methylation between DCIS and invasive breast cancer were confirmed. Further, the functional relevance of these genes’ regulation by methylation was demonstrated in early stage breast cancers from The Cancer Genome Atlas database. This work contributes to the understanding of epigenetic alterations that occur in DCIS and illustrates the potential of DNA methylation as markers of DCIS progression.

2015-06-01 | GSE66313 | GEO

Genome-wide DNA methylation profiles in progression to in situ and invasive carcinoma of the breast with impact on gene transcription and prognosis

Project description:Ductal carcinoma in situ (DCIS) of the breast is a precursor of invasive breast carcinoma (IBC). DNA methylation alterations are thought to be an early event in progression of cancer, and may prove valuable as a tool in clinical decision making and for understanding neoplastic development. Genome-wide DNA methylation profiles of 285 breast tissue samples representing progression of cancer were generated using Illumina HumanMethylation450. Validation of methylation changes between normal and DCIS was performed in an independent dataset of 15 normal and 40 DCIS samples, and validation of a prognostic signature was performed on 583 breast cancer samples from The Cancer Genome Atlas. Using two independent datasets of normal breast tissue and DCIS revealed that DNA methylation profiles of DCIS were radically altered compared to normal breast tissue, involving almost 7000 genes (including CUL7 and ICAM2). Changes between DCIS and IBC involved around 1000 genes. In tumors, DNA methylation was associated with gene expression of almost 3000 genes (p<0.05, Bonferroni corrected) including both negative and positive correlations. A prognostic signature based on methylation level of 18 CpGs (representing genes such as IRF6, TBX5, ZNF259, KCTD21, EPN3, MACF1 and CSNK1G2) was associated to survival of breast cancer patients with invasive tumors, as well as to survival of patients with DCIS and mixed lesions of DCIS and IBC. This work demonstrates that changes in the epigenome occurs early in the neoplastic progression, provide evidence for the possible utilization of DNA methylation based markers of progression in the clinic, and highlights the importance of epigenetic changes in carcinogenesis. Bisulphite converted DNA from the 285 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip

2014-08-08 | E-GEOD-60185 | biostudies-arrayexpress

Genome-wide DNA methylation profiles in progression to in situ and invasive carcinoma of the breast with impact on gene transcription and prognosis

2014-08-08 | GSE60185 | GEO

DNA methylation arrays for 8 Surgical specimens (DNA extracted from FFPE slides) after cetuximab treatment

Project description:DNA methylation arrays for 8 Surgical specimens(DNA extracted from FFPE slides) after cetuximab treatment

2020-01-17 | GSE110995 | GEO

Breast tumor DNA methylation

Project description:Using primary breast tumors from 162 women from the Kaiser Division of Research Pathways Study and the Illumina GoldenGate methylation bead-array platform, we measured CpG loci associated with cancer-related genes 162 tumor specimens from the initial diagnostic biopsy were obtained from the KPNC tumor biorepository for methylation analysis. All tumor specimens were from patients who did not receive neoadjuvant chemotherapy.

2010-07-29 | GSE22290 | GEO

Gene expression profiling of patient's DCIS-IDC tandem lesions by RNA sequencing analysis

Project description:Tandem DCIS/IDC are defined as ductal carcicnoma in situ (DCIS) lesions that have concurrent invasive ductal carcinoma (IDC) within the same breast. These are identified radiologically by an area of clustered microcalcifications adjacent to (contiguous with) an invasive mass. Our radiologist (Dr. William P. Smith) has provided us with biopsy cores from each region. One core from each region (DCIS and IDC) has bas been collected and subjected to RNA sequencing for our studies to compare changes from DCIS to IDC in each individual patient.

2015-02-26 | GSE66301 | GEO

Methylation analysis of cancer and control samples.

Project description:DNA methylation profiling of cancer and control samples. The Illumina GoldenGate Methylation Cancer Panel I was used to obtain DNA methylation profiles across 1,505 CpG sites CpGs distributed across 807 genes in blood DNA specimens.

2012-11-01 | GSE33614 | GEO

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