Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA181273 | ENA |
REPOSITORIES: ENA
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Project description:The aim of this study was to establish a single-cell array comparative genomic hybridization (SCaCGH) method providing in-depth genomic analysis of circulating tumor cells (CTCs) and disseminated tumor cells (DTCs). The robustness and resolution limits of the method were estimated with different cell amounts of the breast cancer cell line SKBR3 using 44k and 244k arrays. Subsequent adjustments of the method were conducted analyzing the copy number profiles of 28 CTCs in combination with four hematopoietic cell (HC) controls from eight metastatic patients and of 24 DTCs, three probable HCs, and five HC controls from seven breast cancer patients and one healthy donor. The frequency of the major genomic gains and losses of the analyzed DTC revealed similarities to primary breast tumor samples with some evident differences. Three of the patients had available profiles for DTC and the corresponding primary tumor. In 2/3 of the examined DTCs, equivalent genomic changes and common aberration breakpoints were disclosed, both to each other and to the corresponding primary tumors. Interestingly, similar copy number changes were found in DTCs taken at time of diagnosis or in DTCs collected at 3-years relapse-free follow up. Residual immunomorphological characterized tumor cells showed balanced profiles with only minor aberrations. Three cells with unclear morphological identification showed either balanced profiles (n=2) or aberrations comparable to the primary tumor and DTC (n=1). SCaCGH may be a powerful tool for molecular characterisation of immunostained and morphological identified CTCs and DTCs to explore the malignant potential, therapeutic targets and tumor heterogeneity of single tumor cells. 24 DTCs, 3 probable HCs, and 5 HCs from 7 early-stage breast cancer patients, 28 CTCs and 4 HCs from 8 metastatic breast cancer patients, and 1 healthy donor were analysed. Comparison with the primary tumor was done in 3 patients. The reference for the patients was DNA from multiple anonymous female donors. This submission does not include the SKBR3 data obtained from the 44k array.
2012-11-19 | E-GEOD-27574 | biostudies-arrayexpress
Project description:The aim of this study was to establish a single-cell array comparative genomic hybridization (SCaCGH) method providing in-depth genomic analysis of circulating tumor cells (CTCs) and disseminated tumor cells (DTCs). The robustness and resolution limits of the method were estimated with different cell amounts of the breast cancer cell line SKBR3 using 44k and 244k arrays. Subsequent adjustments of the method were conducted analyzing the copy number profiles of 28 CTCs in combination with four hematopoietic cell (HC) controls from eight metastatic patients and of 24 DTCs, three probable HCs, and five HC controls from seven breast cancer patients and one healthy donor. The frequency of the major genomic gains and losses of the analyzed DTC revealed similarities to primary breast tumor samples with some evident differences. Three of the patients had available profiles for DTC and the corresponding primary tumor. In 2/3 of the examined DTCs, equivalent genomic changes and common aberration breakpoints were disclosed, both to each other and to the corresponding primary tumors. Interestingly, similar copy number changes were found in DTCs taken at time of diagnosis or in DTCs collected at 3-years relapse-free follow up. Residual immunomorphological characterized tumor cells showed balanced profiles with only minor aberrations. Three cells with unclear morphological identification showed either balanced profiles (n=2) or aberrations comparable to the primary tumor and DTC (n=1). SCaCGH may be a powerful tool for molecular characterisation of immunostained and morphological identified CTCs and DTCs to explore the malignant potential, therapeutic targets and tumor heterogeneity of single tumor cells.
2012-11-19 | GSE27574 | GEO
Project description:Circulating (CTCs) and disseminated (DTCs) tumor cells are of great interest to the field of cancer research as they provide a minimally-invasive window for assessing aspects of cancer biology including tumor heterogeneity, a means to discover biomarkers of disease behavior, and a way to identify and prioritize therapeutic targets in the emerging era of precision oncology. However, the rarity of CTC/DTC poses a significant challenge to the consistent success in analyzing the molecular features of these cells including genomic aberrations. Herein, we demonstrate our optimized and robust methods to reproducibly detect genomic copy number alterations in samples of 2-40 cells after whole-genome amplification using a high resolution SNP-array platform and refined computational algorithms. We have determined the limit of detection for heterogeneity within a sample as 50% and also demonstrated success in analyzing single cells. We validated the genes in genomic regions that are frequently amplified or deleted by qPCR and nCounter copy number quantification. We further applied these methods to DTCs isolated from individuals with advanced prostate cancer to confirm the highly aberrant nature of these cells. We compared copy number alterations of DTCs to matched metastatic tumors isolated from the same individual to gain biological insight. These developments provide high-resolution genomic profiling of single and rare cell populations, and should be applicable to a wide-range of sample sources.
2015-10-02 | GSE73180 | GEO
Project description:Circulating tumor cells (CTCs) and disseminated tumour cells with mesenchymal traits are difficult to detect by epithelial marker proteins. Particularly, triple negative breast cancers (TNBC) that are prone to therapy failure release a subpopulation of circulating tumour cells (CTCs) with mesenchymal traits. To provide tools that support their detection and analysis, the cell line BC-M1 established from disseminated tumour cells in the bone marrow of a breast cancer patient and a bone metastasis subline of MDA-MB-231 were analysed. Mass spectrometry analysis revealed high levels of CUB domain-containing protein 1 (CDCP1) in BC-M1. CDCP1 was found in other carcinoma cell lines (MDA-MB-231, MDA-MB-468) and other DTC cell lines (LC-M1, PC-E1) as well. Peripheral blood mononuclear cells were virtually negative for CDCP1 by Western Blot and immunofluorescent staining. Presence of CDCP1 in CTCs was confirmed by CellSearch. Here, CDCP1 positive CTCs were detected in eight of 30 analysed breast cancer patients. For the isolation of CTCs from the blood of breast cancer patients, we established a sandwich magnetic-activated cell sorting (MACS). The extracellular domain of CDCP1 served for cell catching and the cytoplasmic domain of CDCP1 for immunofluorescent detection of CDCP1 in CTCs. We showed that the MACS approach is suitable for the isolation of EpCam/keratin negative breast cancer cells from the blood and isolated CDCP1 positive CTCs from breast cancer patients by MACS. Hence, our approach is particularly suited for the detection and isolation of CTCs from TNBC when low EpCam or keratin levels limit the application of conventional approaches.
2023-03-20 | PXD035203 | Pride
Project description:Recent technological advances have made it possible to detect circulating breast cancer cells as precursors of distant metastasis and as prognosis marker in nonmetastatic breast cancer patients. Association of circulating tumor cells (CTCs) with molecular alteration in the primary tumor is not widely explored. We reported differential profile of altered genome, copy number alteration and copy-neutral loss of heterogeneity in 14 primary tumors when comparing patients with CTCs+ versus CTCs- using single-nucleotide polymorphism array. The most prevalent copy number alteration in CTCs+ patients was at 8q and particularly at the cytoband 8q24 (MYC loci). As the role of MYC in the process of tumor cell invasion and migration is controversial, we further validated in a larger series of patients whether altered MYC (amplification or gained) in primary tumors was correlated with the presence of CTCs in peripheral blood (as a surrogate of micrometastais). No correlation between MYC alteration and presence of CTCs was observed, providing clinical support to the recent data that MYC suppresses cancer metastasis or at least suggesting that MYC alteration could be contributory but insufficient for the generation of CTCs. This molecular association needs to be further characterized in preclinical model and especially clinically. We analyzed CN and LOH of CTC+ and CTC-
2014-11-19 | E-GEOD-43149 | biostudies-arrayexpress
Project description:High-resolution copy number analysis of medulloblastoma
| PRJNA111773 | ENA
Project description:Recent technological advances have made it possible to detect circulating breast cancer cells as precursors of distant metastasis and as prognosis marker in nonmetastatic breast cancer patients. Association of circulating tumor cells (CTCs) with molecular alteration in the primary tumor is not widely explored. We reported differential profile of altered genome, copy number alteration and copy-neutral loss of heterogeneity in 14 primary tumors when comparing patients with CTCs+ versus CTCs- using single-nucleotide polymorphism array. The most prevalent copy number alteration in CTCs+ patients was at 8q and particularly at the cytoband 8q24 (MYC loci). As the role of MYC in the process of tumor cell invasion and migration is controversial, we further validated in a larger series of patients whether altered MYC (amplification or gained) in primary tumors was correlated with the presence of CTCs in peripheral blood (as a surrogate of micrometastais). No correlation between MYC alteration and presence of CTCs was observed, providing clinical support to the recent data that MYC suppresses cancer metastasis or at least suggesting that MYC alteration could be contributory but insufficient for the generation of CTCs. This molecular association needs to be further characterized in preclinical model and especially clinically.
2014-11-19 | GSE43149 | GEO
Project description:In addition to KIT and PDGFRA mutations, sequential accumulation of other genetic events is involved in the development and progression of gastrointestinal stromal tumors (GISTs). Until recently, the significance of these other alterations has not been thoroughly investigated. The combination of gene expression profiling and high-resolution genomic copy number analysis offers a detailed molecular portrait of GISTs, providing an essential comprehensive knowledge necessary to guide the discovery of novel target genes involved in tumor development and progression. Fresh tissue specimens from 25 patients with GIST were collected and high-resolution genomic copy number analyses were performed using Affymetrix SNP array 6.0. GIST tumor samples from mutated (KIT or PDGFRA) or Wild Type patients were labeled for hybridization on Affymetrix microarrays. Copy number analysis of Affymetrix SNP6.0 arrays was performed for 25 GIST samples, then compared to gene expression data.
2010-08-27 | E-GEOD-20709 | biostudies-arrayexpress
Project description:We developed a novel approach to isolate tumor cells with high purity from blood via immunomagnetic enrichment followed by fluorescence activated cell sorting (IE/FACS) and examined copy number alterations in these cells. Magnetic beads coated with EpCAM mAb were added to blood to enrich for tumor cells. Enriched samples were then subjected to FACS analysis using differentially labeled mAbs to distinguish tumor cells (EpCAM+) from leukocytes (CD45+) during sorting. DNA from isolated tumor cells was subjected to whole genome amplification (WGA) and copy number analysis via array comparative genomic hybridization (CGH). The assay was evaluated using BT474 and MCF7 breast cancer cell lines and in CTCs from 5 metastatic breast cancer (MBC) patients with matched archival primary tumors and later extended to an additional 97 MBC patients. Evaluation of the assay on isolated breast cancer cell lines spiked into blood correctly identified the known genomic alterations with high reproducibility. In clinical studies, comparison of CTCs with matched archival primary tumors confirmed shared lineage with notable divergence. In addition, serial testing of CTCs confirmed reproducibility, and indicated genomic change over time. Analysis of genomic profiles of CTCs from 102 MBC patients revealed common copy number alterations including gains in 1q and 8q and losses in 8p and 11q. Comparison with a published CGH dataset of primary breast tumors revealed similar frequencies of recurrent genomic copy number aberrations.
2012-12-31 | E-GEOD-27511 | biostudies-arrayexpress
Project description:High-resolution aCGH analyses of copy number alterations in HER2-amplified breast cancer
| PRJNA126281 | ENA