Journal Article
. 2018 Sep; 7:.
doi: 10.7554/eLife.37294.

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

Haley Hieronymus 1 Rajmohan Murali 2 Amy Tin 3 Kamlesh Yadav 4 Wassim Abida 1 Henrik Moller 5 Daniel Berney 6 Howard Scher 7 Brett Carver 8 Peter Scardino 8 Nikolaus Schultz 9 Barry Taylor 1 Andrew Vickers 3 Jack Cuzick 10 Charles L Sawyers 1 
Affiliations
  • PMID: 30178746
  •     43 References
  •     63 citations

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.

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