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...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2018-09-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/37294 |
| _version_ | 1811253259895046144 |
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| author | Haley Hieronymus Rajmohan Murali Amy Tin Kamlesh Yadav Wassim Abida Henrik Moller Daniel Berney Howard Scher Brett Carver Peter Scardino Nikolaus Schultz Barry Taylor Andrew Vickers Jack Cuzick Charles L Sawyers |
| author_facet | Haley Hieronymus Rajmohan Murali Amy Tin Kamlesh Yadav Wassim Abida Henrik Moller Daniel Berney Howard Scher Brett Carver Peter Scardino Nikolaus Schultz Barry Taylor Andrew Vickers Jack Cuzick Charles L Sawyers |
| author_sort | Haley Hieronymus |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T16:48:17Z |
| format | Article |
| id | doaj.art-9bb98e789ff74231b7de3a9771793c64 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:48:17Z |
| publishDate | 2018-09-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-9bb98e789ff74231b7de3a9771793c642022-12-22T03:24:31ZengeLife Sciences Publications LtdeLife2050-084X2018-09-01710.7554/eLife.37294Tumor copy number alteration burden is a pan-cancer prognostic factor associated with recurrence and deathHaley Hieronymus0Rajmohan Murali1https://orcid.org/0000-0001-6988-4295Amy Tin2Kamlesh Yadav3Wassim Abida4Henrik Moller5Daniel Berney6Howard Scher7Brett Carver8Peter Scardino9Nikolaus Schultz10Barry Taylor11Andrew Vickers12Jack Cuzick13Charles L Sawyers14https://orcid.org/0000-0003-4955-6475Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, United StatesDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, United StatesDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, United StatesDepartment of Urology, Icahn School of Medicine at Mount Sinai, New York, United StatesHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, United States; Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, United StatesDepartment of Cancer Epidemiology, Population and Global Health, King's College London, London, United KingdomDepartment of Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, United KingdomGenitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, United States; Department of Medicine, Weill Cornell Medical College, New York, United StatesDepartment of Urology, Memorial Sloan Kettering Cancer Center, New York, United StatesDepartment of Urology, Memorial Sloan Kettering Cancer Center, New York, United StatesMarie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, United StatesHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, United States; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, United States; Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, United StatesDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, United StatesCentre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United KingdomHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, United States; Howard Hughes Medical Institute, Chevy Chase, United StatesThe 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.https://elifesciences.org/articles/37294prostate cancergenomicscopy number alteration |
| spellingShingle | Haley Hieronymus Rajmohan Murali Amy Tin Kamlesh Yadav Wassim Abida Henrik Moller Daniel Berney Howard Scher Brett Carver Peter Scardino Nikolaus Schultz Barry Taylor Andrew Vickers Jack Cuzick Charles L Sawyers Tumor copy number alteration burden is a pan-cancer prognostic factor associated with recurrence and death eLife prostate cancer genomics copy number alteration |
| 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 | prostate cancer genomics copy number alteration |
| url | https://elifesciences.org/articles/37294 |
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