Project description:we describe a mRNA profiling analysis of matched ductal carcinoma in situ and invasive duct carcinoma components of FFPE breast carcinomas with the purpose to identify potential prognostic markers mRNA extracted from 15 matched DCIS/IDC and 14 pure DCIS preparations was profiled using Illumina DASL platform
Project description:Ductal carcinoma in situ (DCIS) is a nonobligate precursor of invasive breast cancer. Its biological features, particularly its intratumoral heterogeneity, remain obscure. Moreover, mechanism of lymph node metastasis is unclear. To address this deficiency, we performed single-cell transcriptome profiling of DCIS, invasive ductal carcinoma (IDC) and lymph node metastasis. Single-cell transcriptome analysis revealed that breast cancer exhibits intratumoral heterogeneity at the transcriptional level, defining specific functions, and that DCIS has similar heterogeneity to IDC.
Project description:This is a matched-pair analysis of ductal carcinoma in situ (DCIS) and invasive component (IDC) of nine breast ductal carcinoma to identify novel molecular markers characterizing the transition from DCIS to IDC for a better understanding of its molecular biology.
Project description:This study identifies progression in breast ductal carcinoma in situ (DCIS) as it progresses towards triple negative invasive breast cancer (TNBC). Bulk DNA arrayCGH was performed on the C3Tag genetically engineered mouse model that forms human breast-like DCIS and TNBC.
Project description:This is a matched-pair analysis of ductal carcinoma in situ (DCIS) and invasive component (IDC) of nine breast ductal carcinoma to identify novel molecular markers characterizing the transition from DCIS to IDC for a better understanding of its molecular biology. Keywords: Affymetrix-based Microarrays in Mamma carcinoma
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.
Project description:Concordance of DNA methylation profiles between breast core biopsy and surgical excision specimens containing ductal carcinoma in situ (DCIS)
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
