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Tumor copy number alteration burden is a pan-cancer prognostic factor associated with recurrence and death
The level of copy number alteration (CNA), termed CNA burden, in the tumor genome is associated with recurrence of primary prostate cancer. Whether CNA burden is associated with prostate cancer survival or outcomes in other cancers is unknown. We analyzed the CNA landscape of conservatively treated...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6145837/ https://www.ncbi.nlm.nih.gov/pubmed/30178746 http://dx.doi.org/10.7554/eLife.37294 |
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author | Hieronymus, Haley Murali, Rajmohan Tin, Amy Yadav, Kamlesh Abida, Wassim Moller, Henrik Berney, Daniel Scher, Howard Carver, Brett Scardino, Peter Schultz, Nikolaus Taylor, Barry Vickers, Andrew Cuzick, Jack Sawyers, Charles L |
author_facet | Hieronymus, Haley Murali, Rajmohan Tin, Amy Yadav, Kamlesh Abida, Wassim Moller, Henrik Berney, Daniel Scher, Howard Carver, Brett Scardino, Peter Schultz, Nikolaus Taylor, Barry Vickers, Andrew Cuzick, Jack Sawyers, Charles L |
author_sort | Hieronymus, Haley |
collection | PubMed |
description | The level of copy number alteration (CNA), termed CNA burden, in the tumor genome is associated with recurrence of primary prostate cancer. Whether CNA burden is associated with prostate cancer survival or outcomes in other cancers is unknown. We analyzed the CNA landscape of conservatively treated prostate cancer in a biopsy and transurethral resection cohort, reflecting an increasingly common treatment approach. We find that CNA burden is prognostic for cancer-specific death, independent of standard clinical prognosticators. More broadly, we find CNA burden is significantly associated with disease-free and overall survival in primary breast, endometrial, renal clear cell, thyroid, and colorectal cancer in TCGA cohorts. To assess clinical applicability, we validated these findings in an independent pan-cancer cohort of patients whose tumors were sequenced using a clinically-certified next generation sequencing assay (MSK-IMPACT), where prognostic value varied based on cancer type. This prognostic association was affected by incorporating tumor purity in some cohorts. Overall, CNA burden of primary and metastatic tumors is a prognostic factor, potentially modulated by sample purity and measurable by current clinical sequencing. |
format | Online Article Text |
id | pubmed-6145837 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-61458372018-09-20 Tumor copy number alteration burden is a pan-cancer prognostic factor associated with recurrence and death Hieronymus, Haley Murali, Rajmohan Tin, Amy Yadav, Kamlesh Abida, Wassim Moller, Henrik Berney, Daniel Scher, Howard Carver, Brett Scardino, Peter Schultz, Nikolaus Taylor, Barry Vickers, Andrew Cuzick, Jack Sawyers, Charles L eLife Cancer Biology The level of copy number alteration (CNA), termed CNA burden, in the tumor genome is associated with recurrence of primary prostate cancer. Whether CNA burden is associated with prostate cancer survival or outcomes in other cancers is unknown. We analyzed the CNA landscape of conservatively treated prostate cancer in a biopsy and transurethral resection cohort, reflecting an increasingly common treatment approach. We find that CNA burden is prognostic for cancer-specific death, independent of standard clinical prognosticators. More broadly, we find CNA burden is significantly associated with disease-free and overall survival in primary breast, endometrial, renal clear cell, thyroid, and colorectal cancer in TCGA cohorts. To assess clinical applicability, we validated these findings in an independent pan-cancer cohort of patients whose tumors were sequenced using a clinically-certified next generation sequencing assay (MSK-IMPACT), where prognostic value varied based on cancer type. This prognostic association was affected by incorporating tumor purity in some cohorts. Overall, CNA burden of primary and metastatic tumors is a prognostic factor, potentially modulated by sample purity and measurable by current clinical sequencing. eLife Sciences Publications, Ltd 2018-09-04 /pmc/articles/PMC6145837/ /pubmed/30178746 http://dx.doi.org/10.7554/eLife.37294 Text en © 2018, Hieronymus et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Cancer Biology Hieronymus, Haley Murali, Rajmohan Tin, Amy Yadav, Kamlesh Abida, Wassim Moller, Henrik Berney, Daniel Scher, Howard Carver, Brett Scardino, Peter Schultz, Nikolaus Taylor, Barry Vickers, Andrew Cuzick, Jack Sawyers, Charles L Tumor copy number alteration burden is a pan-cancer prognostic factor associated with recurrence and death |
title | Tumor copy number alteration burden is a pan-cancer prognostic factor associated with recurrence and death |
title_full | Tumor copy number alteration burden is a pan-cancer prognostic factor associated with recurrence and death |
title_fullStr | Tumor copy number alteration burden is a pan-cancer prognostic factor associated with recurrence and death |
title_full_unstemmed | Tumor copy number alteration burden is a pan-cancer prognostic factor associated with recurrence and death |
title_short | Tumor copy number alteration burden is a pan-cancer prognostic factor associated with recurrence and death |
title_sort | tumor copy number alteration burden is a pan-cancer prognostic factor associated with recurrence and death |
topic | Cancer Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6145837/ https://www.ncbi.nlm.nih.gov/pubmed/30178746 http://dx.doi.org/10.7554/eLife.37294 |
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