ABSTRACT: Concordance of DNA methylation profiles between breast core biopsy and surgical excision specimens containing ductal carcinoma in situ (DCIS)
Project description: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.
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. 6 pairs of DCIS-IDC samples were collected, and analysed by RNA sequencing
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.
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 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 non-invasive form of breast cancer where cells restricted to the ducts exhibit an atypical phenotype. Some DCIS lesions are believed to rapidly transit to invasive ductal carcinomas (IDCs), while others remain unchanged. Existing classification systems for DCIS fail to identify those lesions that transit to IDC. We studied gene expression patterns of 31 pure DCIS, 36 pure invasive cancers and 42 cases of mixed diagnosis (invasive cancer with an in situ component) using Agilent Whole Human Genome Oligo Microarrays 44k. Six normal breast tissue samples were also included as controls. qRT-PCR was used for validation. All DCIS and invasive samples could be classified into the intrinsic molecular subtypes defined for invasive breast cancer. Hierarchical clustering establishes that samples group by intrinsic subtype, and not by diagnosis. We observed heterogeneity in the transcriptomes among DCIS of high histological grade and identified a distinct subgroup containing seven of the 31 DCIS samples with gene expression characteristics more similar to advanced tumours. A set of genes independent of grade, ER-status and HER2-status was identified by logistic regression that univariately classified a sample as belonging to this distinct DCIS subgroup. qRT-PCR of single markers clearly separated this DCIS subgroup from the other DCIS, and contains samples from several histopathological and intrinsic molecular subtypes. The genes that differentiate between these two types of DCIS suggest several processes related to the re-organisation of the microenvironment. This raises interesting possibilities for identification of DCIS lesions both with and without invasive characteristics, which potentially could be used in clinical assessment of a woman's risk of progression, and lead to improved management that would avoid the current over- and under-treatment of patients. Breast cancer samples, 31 pure DCIS patients, 36 IDC patients, 42 mixed and 6 normal.
Project description:Ductal carcinoma in situ (DCIS) is the presence of abnormal cells inside a milk duct in the breast. DCIS is considered the earliest form of breast cancer. DCIS is noninvasive, meaning that it does not spread out of the milk duct and has a low risk of becoming invasive.
Project description:This study identifies progression in breast ductal carcinoma in situ (DCIS) as it progresses towards triple negative invasive breast cancer (TNBC).
Project description:This study identifies progression in breast ductal carcinoma in situ (DCIS) as it progresses towards triple negative invasive breast cancer (TNBC).
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.
