Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA297628 | ENA |
REPOSITORIES: ENA
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Project description:Disseminated epithelial cells can be isolated from the bone marrow of a far greater frac-tion of prostate-cancer patients than the fraction of patients who progress to metastatic disease. To provide a better understanding of these cells, we have characterized their genomic altera-tions. We first present an array comparative genomic hybridization method capable of detecting genomic changes in the small number of disseminated cells (10-20) that can typically be ob-tained from bone-marrow aspirates of prostate-cancer patients. We show multiple regions of copy-number change, including alterations common in prostate cancer, such as 8p loss, 8q gain, and gain encompassing the androgen-receptor gene on Xq, in the disseminated cell pools from 11 metastatic patients. We found fewer and less striking genomic alterations in the 48 pools of disseminated cells from patients with organ-confined disease. However, we identify changes shared by these samples with their corresponding primary tumors and prostate-cancer altera-tions reported in the literature, evidence that these cells, like those in advanced disease, are disseminated tumor cells (DTCs). We also demonstrate that DTCs from patients with advanced and localized disease share several abnormalities, including losses containing cell-adhesion genes and alterations reported to associate with progressive disease. These shared alterations might confer the capability to disseminate or establish secondary disease. Overall, the spectrum of genomic deviations is evidence for metastatic capacity in advanced-disease DTCs and varia-tion in that capacity in DTCs from localized disease. Our analysis lays the foundation for eluci-dation of the relationship between DTC genomic alterations and progressive prostate cancer. Keywords: array comparative genomic hybridization, prostate cancer, disseminated cells
2008-08-17 | GSE11155 | GEO
Project description:Genomic alterations indicate tumor origin and varied metastatic potential of disseminated cells from prostate cancer
| PRJNA106959 | ENA
Project description:Tumor Cell Heterogeneity and Dormancy in Single Disseminated Prostate Cancer Cells
| PRJNA212632 | ENA
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:High-resolution analysis of copy number changes in circulating and disseminated tumor cells in breast cancer patients
| PRJNA181273 | ENA
Project description:Tumor heterogeneity may reduce the efficacy of molecularly guided systemic therapy for cancers that have metastasized. To determine whether the genomic alterations in a single metastasis provide a reasonable assessment of the major oncogenic drivers of other dispersed metastases in an individual, we analyzed multiple tumors from men with disseminated prostate cancer through whole-exome sequencing, array comparative genomic hybridization (CGH) and RNA transcript profiling, and we compared the genomic diversity within and between individuals.
2016-02-16 | GSE77930 | GEO
Project description:Gene expression profiling of disseminated tumor cells in lung, lung metastatses and residual tumor cells in the MMTV-PyMT breast cancer model. Profiling gene expression change between disseminated tumor cells, lung metastases and residual tumor cells from the MMTV-PyMT breast cancer model.
2013-01-18 | E-GEOD-43566 | biostudies-arrayexpress
Project description:Prostate cancer (PCa) disseminated tumor cells (DTC) in the bone marrow (BM) can remain dormant for prolonged periods before recurrence. Our aim was to characterize individual prostate DTC, analyze tumor cell heterogeneity, and identify markers of tumor dormancy. Custom Agilent 44K whole human genome expression oligonucleotide microarrays were used to profile single disseminated tumor cells isolated from bone marrow (BM) samples of four patients with no evidence of disease (NED) upon follow-up and six advanced disease (ADV) prostate cancer patients. Essentially, a two-step selection process was employed, in which anti-CD45 and anti-CD61 conjugated to immunomagnetic beads were used for negative selection, and anti-HEA was used for positive selection. Cells were then fluorescently stained for BerEP4, counter stained with RPE anti-CD45, and individually selected (10 single cells each per patient) under fluorescent light using a micropipette system for further analysis. RNA was amplified using the WT-Oviation one-direct system and hybridized against a common reference pool of prostate tumor cell lines.
2014-09-16 | E-GEOD-48995 | biostudies-arrayexpress
Project description:Prostate cancer (PCa) disseminated tumor cells (DTC) in the bone marrow (BM) can remain dormant for prolonged periods before recurrence. Our aim was to characterize individual prostate DTC, analyze tumor cell heterogeneity, and identify markers of tumor dormancy.
2014-09-16 | GSE48995 | GEO
Project description:Intraindividual tumor heterogeneity may reduce the efficacy of molecularly guided systemic therapy for cancers that have metastasized. To determine whether the genomic alterations in a single metastasis provide a reasonable assessment of the major oncogenic drivers of other dispersed metastases in an individual, we analyzed multiple tumors from men with disseminated prostate cancer through whole-exome sequencing, array comparative genomic hybridization (CGH) and RNA transcript profiling [GSE74685], and we compared the genomic diversity within and between individuals. Custom Agilent 44K whole human genome expression oligonucleotide microarrays were used to profile 171 CRPC tumors from 63 patients. RNA was amplified prior to hybridization against a common reference pool of prostate tumor cell lines. Custom Agilent 415K whole human CGH microarrays were used to profile 149 CRPC tumors from 60 patients. Genomic DNA from tumors was hybridized against a pool of reference normal male DNA.
2016-02-16 | E-GEOD-77930 | biostudies-arrayexpress