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Elife. 2018 Sep 4;7. pii: e37294. doi: 10.7554/eLife.37294.

Tumor copy number alteration burden is a pan-cancer prognostic factor associated with recurrence and death.

Author information

1
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, United States.
2
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, United States.
3
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, United States.
4
Department of Urology, Icahn School of Medicine at Mount Sinai, New York, United States.
5
Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, United States.
6
Department of Cancer Epidemiology, Population and Global Health, King's College London, London, United Kingdom.
7
Department of Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom.
8
Department of Medicine, Weill Cornell Medical College, New York, United States.
9
Department of Urology, Memorial Sloan Kettering Cancer Center, New York, United States.
10
Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, United States.
11
Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom.
12
Howard Hughes Medical Institute, Chevy Chase, United States.

Abstract

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.

KEYWORDS:

cancer biology; copy number alteration; genomics; human; human biology; medicine; prostate cancer

PMID:
30178746
PMCID:
PMC6145837
DOI:
10.7554/eLife.37294
[Indexed for MEDLINE]
Free PMC Article

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