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Isolation and genomic analysis of circulating tumor cells from castration resistant metastatic prostate cancer
BACKGROUND: The number of circulating tumor cells (CTCs) in metastatic prostate cancer patients provides prognostic and predictive information. However, it is the molecular characterization of CTCs that offers insight into the biology of these tumor cells in the context of personalized treatment. ME...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3395839/ https://www.ncbi.nlm.nih.gov/pubmed/22373240 http://dx.doi.org/10.1186/1471-2407-12-78 |
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author | Magbanua, Mark Jesus M Sosa, Eduardo V Scott, Janet H Simko, Jeff Collins, Colin Pinkel, Dan Ryan, Charles J Park, John W |
author_facet | Magbanua, Mark Jesus M Sosa, Eduardo V Scott, Janet H Simko, Jeff Collins, Colin Pinkel, Dan Ryan, Charles J Park, John W |
author_sort | Magbanua, Mark Jesus M |
collection | PubMed |
description | BACKGROUND: The number of circulating tumor cells (CTCs) in metastatic prostate cancer patients provides prognostic and predictive information. However, it is the molecular characterization of CTCs that offers insight into the biology of these tumor cells in the context of personalized treatment. METHODS: We developed a novel approach to isolate CTCs away from hematopoietic cells with high purity, enabling genomic analysis of these cells. The isolation protocol involves immunomagnetic enrichment followed by fluorescence activated cell sorting (IE/FACS). To evaluate the feasibility of isolation of CTCs by IE/FACS and downstream genomic profiling, we conducted a pilot study in patients with metastatic castration resistant prostate cancer (CRPC). Twenty (20) sequential CRPC patients were assayed using CellSearch™. Twelve (12) patients positive for CTCs were subjected to immunomagnetic enrichment and fluorescence activated cell sorting (IE/FACS) to isolate CTCs. Genomic DNA of CTCs was subjected to whole genome amplification (WGA) followed by gene copy number analysis via array comparative genomic hybridization (aCGH). RESULTS: CTCs from nine (9) patients successfully profiled were observed to have multiple copy number aberrations including those previously reported in primary prostate tumors such as gains in 8q and losses in 8p. High-level copy number gains at the androgen receptor (AR) locus were observed in 7 (78%) cases. Comparison of genomic profiles between CTCs and archival primary tumors from the same patients revealed common lineage. However, high-level copy number gains in the AR locus were observed in CTCs, but not in the matched archival primary tumors. CONCLUSIONS: We developed a new approach to isolate prostate CTCs without significant leukocyte admixture, and to subject them to genome-wide copy number analysis. Our assay may be utilized to explore genomic events involved in cancer progression, e.g. development of castration resistance and to monitor therapeutic efficacy of targeted therapies in clinical trials in a relatively non-invasive manner. |
format | Online Article Text |
id | pubmed-3395839 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-33958392012-07-16 Isolation and genomic analysis of circulating tumor cells from castration resistant metastatic prostate cancer Magbanua, Mark Jesus M Sosa, Eduardo V Scott, Janet H Simko, Jeff Collins, Colin Pinkel, Dan Ryan, Charles J Park, John W BMC Cancer Technical Advance BACKGROUND: The number of circulating tumor cells (CTCs) in metastatic prostate cancer patients provides prognostic and predictive information. However, it is the molecular characterization of CTCs that offers insight into the biology of these tumor cells in the context of personalized treatment. METHODS: We developed a novel approach to isolate CTCs away from hematopoietic cells with high purity, enabling genomic analysis of these cells. The isolation protocol involves immunomagnetic enrichment followed by fluorescence activated cell sorting (IE/FACS). To evaluate the feasibility of isolation of CTCs by IE/FACS and downstream genomic profiling, we conducted a pilot study in patients with metastatic castration resistant prostate cancer (CRPC). Twenty (20) sequential CRPC patients were assayed using CellSearch™. Twelve (12) patients positive for CTCs were subjected to immunomagnetic enrichment and fluorescence activated cell sorting (IE/FACS) to isolate CTCs. Genomic DNA of CTCs was subjected to whole genome amplification (WGA) followed by gene copy number analysis via array comparative genomic hybridization (aCGH). RESULTS: CTCs from nine (9) patients successfully profiled were observed to have multiple copy number aberrations including those previously reported in primary prostate tumors such as gains in 8q and losses in 8p. High-level copy number gains at the androgen receptor (AR) locus were observed in 7 (78%) cases. Comparison of genomic profiles between CTCs and archival primary tumors from the same patients revealed common lineage. However, high-level copy number gains in the AR locus were observed in CTCs, but not in the matched archival primary tumors. CONCLUSIONS: We developed a new approach to isolate prostate CTCs without significant leukocyte admixture, and to subject them to genome-wide copy number analysis. Our assay may be utilized to explore genomic events involved in cancer progression, e.g. development of castration resistance and to monitor therapeutic efficacy of targeted therapies in clinical trials in a relatively non-invasive manner. BioMed Central 2012-02-28 /pmc/articles/PMC3395839/ /pubmed/22373240 http://dx.doi.org/10.1186/1471-2407-12-78 Text en Copyright ©2012 Magbanua et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Technical Advance Magbanua, Mark Jesus M Sosa, Eduardo V Scott, Janet H Simko, Jeff Collins, Colin Pinkel, Dan Ryan, Charles J Park, John W Isolation and genomic analysis of circulating tumor cells from castration resistant metastatic prostate cancer |
title | Isolation and genomic analysis of circulating tumor cells from castration resistant metastatic prostate cancer |
title_full | Isolation and genomic analysis of circulating tumor cells from castration resistant metastatic prostate cancer |
title_fullStr | Isolation and genomic analysis of circulating tumor cells from castration resistant metastatic prostate cancer |
title_full_unstemmed | Isolation and genomic analysis of circulating tumor cells from castration resistant metastatic prostate cancer |
title_short | Isolation and genomic analysis of circulating tumor cells from castration resistant metastatic prostate cancer |
title_sort | isolation and genomic analysis of circulating tumor cells from castration resistant metastatic prostate cancer |
topic | Technical Advance |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3395839/ https://www.ncbi.nlm.nih.gov/pubmed/22373240 http://dx.doi.org/10.1186/1471-2407-12-78 |
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