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Single-nucleotide polymorphism array analysis reveals distinct chromosomal aberrations in breast cancer tumors according to the circulating tumor cells status

ABSTRACT: 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).Â 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-

ORGANISM(S): Homo sapiens

SUBMITTER: Lara Nonell

PROVIDER: E-GEOD-43149 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Single-nucleotide polymorphism array analysis reveals distinct chromosomal aberrations in breast cancer tumors according to the circulating tumor cells status

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

Circulating Tumor Cell Clusters are Oligoclonal Precursors of Breast Cancer Metastasis

Project description:Clusters of circulating tumor cells (CTC-clusters) are present in the blood of patients with cancer but their contribution to metastasis is not well defined. Here, we first use mouse models to demonstrate that breast cancer cells injected intravascularly as clusters are more prone to survive and colonize the lungs than single cells. Primary mammary tumors comprised of tagged cells give rise to oligoclonal CTC-clusters, with 50-fold increased metastatic potential, compared with single CTCs. Using intravital imaging and in vivo flow cytometry, CTC-clusters are visualized in the tumor circulation, and they demonstrate rapid clearance in peripheral vessels. In patients with breast cancer, presence of CTC-clusters is correlated with decreased progression-free survival. RNA sequencing identifies the cell junction protein plakoglobin as most differentially expressed between clusters and single human breast CTCs. Expression of plakoglobin is required for efficient CTC-cluster formation and breast cancer metastasis in mice, while its expression is associated with diminished metastasis-free survival in breast cancer patients. Together, these observations suggest that plakoglobin-enriched primary tumor cells break off into the vasculature as CTC-clusters, with greatly enhanced metastasis propensity. RNA-seq from 29 samples (15 pools of single CTCs and 14 CTC-clusters) isolated from 10 breast cancer patients

2014-07-11 | E-GEOD-51827 | biostudies-arrayexpress

Expression data from human Circulating Tumor Cells (CTC) and HT-29 cells

Project description:Unraveling the yet unknown molecular mechanisms regulating the biology of metastasis-competent Circulating Tumor Cells (CTCs) is important for better understanding metastatic growth and disease relapses in patients with colon cancer. We investigated and compared the transcriptome profiles of the CTC line and of a cell line derived from a primary colon cancer to get some insight into the specific molecular mechanism of metastasis-competent CTCs. We used microarrays to establish the molecular portrait of the metastasis-competent CTC and of HT-29 cells

2019-06-02 | GSE82198 | GEO

Next generation sequencing profiling experimental circulating tumor cells-derived metastatic variants [ATAC-seq]

Project description:Hematogenous metastasis is initiated by a subset of circulating tumor cells (CTCs) shed from primary or metastatic tumors into the blood circulation. Thus, CTCs provide a unique patient biopsy resource to decipher the cellular subpopulations that initiate metastasis and their molecular properties. However, one crucial question is whether CTCs derived from patients recapitulate human metastatic disease in an animal model. Here, we show that CTC lines established from breast cancer patients are capable of generating metastases in mice with a pattern recapitulating most major organs from corresponding patients. We used ATAC-seq to assay chromatin accessibility in parental CTC and CTC-derived metastatic cells. Genome-wide sequencing analyses of metastatic variants identified novel chromatin accessibility domains predicting organ-specific metastasis identified from CTCs and facilitate the development of potential therapies targeting metastatis initiating cells in circulation.

2019-10-14 | GSE112852 | GEO

Circulating Tumor Cell Clusters are Oligoclonal Precursors of Breast Cancer Metastasis

2014-07-11 | GSE51827 | GEO

Hexokinase 2 detects cytokeratin negative circulating tumor cells in lung adenocarcinoma

Project description:Circulating tumor cells (CTCs) represent the molecular characteristics of tumor sites and travel in the blood for seeding distant metastases. "EpCAM+/pan-cytokeratin (CK)+/CD45-/DAPI+" has been widely accepted as a CTC definition, especially in breast cancer, prostate cancer and colorectal cancer. However, reports on CTC detection in non-small cell lung cancer are limited due to a lack of efficient CTC marker. We describe hexokinase 2 (HK2) that assays elevated glycolysis of cancer cells, called Warburg effect, as a new marker for CTC detection in lung adenocarcinoma (LUAD), especially the CK negative CTCs. Single-cell sequencing was used to confirm the malignancy of putative CTCs by detecting genome-wide copy number alternations characteristic of malignant cells. We employed this marker in a variety of liquid biopsies from LUAD patients, including peripheral blood, pleural effusion and cerebrospinal fluid.

2021-02-28 | E-MTAB-8767 | biostudies-arrayexpress

Molecular characterization of breast cancer circulating tumor cells (CTCs) associated with brain metastasis

Project description:The enumeration of EpCAM-positive circulating tumor cells (CTCs) has allowed clinicians to estimate the overall metastatic burden in breast cancer patients. However, a thorough understanding of CTCs associated with breast cancer brain metastasis (BCBM) is necessary for early identification and evaluation of treatment response to BCBM. In this study, we report that BCBM CTCs are enriched in a distinct sub-population of cells identifiable by their biomarker expression and mutational content. Here we report the discovery of a unique “CTC gene signature” that is distinct from primary breast cancer tissues. Further dissection of the CTC signature identified signaling pathways associated with BCBM CTCs that may play roles in potentiating BCBM.

2017-05-31 | GSE99394 | GEO

Next generation sequencing profiling experimental circulating tumor cells-derived metastatic variants [RNA-seq]

Project description:Hematogenous metastasis is initiated by a subset of circulating tumor cells (CTCs) shed from primary or metastatic tumors into the blood circulation. Thus, CTCs provide a unique patient biopsy resource to decipher the cellular subpopulations that initiate metastasis and their molecular properties. However, one crucial question is whether CTCs derived from patients recapitulate human metastatic disease in an animal model. Here, we show that CTC lines established from breast cancer patients are capable of generating metastases in mice with a pattern recapitulating most major organs from corresponding patients. Genome-wide sequencing analyses of metastatic variants identified novel organ tropism-associated markers identified from CTCs and facilitate the development of potential therapies targeting metastatis initiating cells in circulation.

2019-10-14 | GSE112855 | GEO

Next generation sequencing profiling experimental circulating tumor cells-derived metastatic variants [micro-environment]

Project description:Hematogenous metastasis is initiated by a subset of circulating tumor cells (CTCs) shed from primary or metastatic tumors into the blood circulation. Thus, CTCs provide a unique patient biopsy resource to decipher the cellular subpopulations that initiate metastasis and their molecular properties. However, one crucial question is whether CTCs derived from patients recapitulate human metastatic disease in an animal model. Here, we show that CTC lines established from breast cancer patients are capable of generating metastases in mice with a pattern recapitulating most major organs from corresponding patients. To investigate the tumor microenvironment changes in different metastases, we used RNA-seq to analyze expression changes in stromal cells after tumor formation in the brain, lung and bone microenvironments relative to control stromal cells from tumor free mice.

2019-10-14 | GSE112853 | GEO

Epigenomic analysis reveals a unique DNA methylation program of metastasis-competent circulating tumor cells in colorectal cancer

Project description:Metastasis is the main cause of cancer-related deaths in patients with solid tumors, including colorectal cancer (CRC). Circulating tumor cells (CTCs) and epigenetic alterations are involved in the development of metastasis. It is important to characterize the DNA methylation pattern of metastasis-competent CTCs to better understand the metastatic process and obtain new clinical applications for cancer patients. Therefore, the aim of this study was to investigate the DNA methylation landscape of metastasis-competent CTCs in CRC. The DNA methylome of the human colorectal cancer-derived cell line CTC-MCC-41 was compared with primary (HT29, Caco2, HCT116, RKO) and metastatic (SW620 and COLO205) CRC cells using a genome-wide methylation analysis.

2023-09-20 | GSE220096 | GEO

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