Paper Spotlight: Genomic Alterations Predictive of Poor Clinical Outcomes in Pan-cancer



October 4, 2022

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  • Oncotarget published this research paper on September 28, 2022 in Volume 13, entitled, "Genomic alterations predictive of poor clinical outcomes in pan-cancer" by researchers from Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL; Miller School of Medicine, University of Miami, Miami, FL; Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA; Broad Institute of MIT, Cambridge, MA; School of Medicine, University of California San Francisco, San Francisco, CA; Dana-Farber Cancer Institute and Brigham and Women’s Hospital, Boston, MA. DOI - Correspondence to - Mohammed Alshalalfa - Abstract Background: Genomic alterations are highly frequent across cancers, but their prognostic impact is not well characterized in pan-cancer cohorts. Here, we use pan-cancer cohorts from TCGA and MSK-IMPACT to evaluate the associations of common genomic alterations with poor clinical outcome. Materials and Methods: Genomic alterations in commonly altered genes were extracted from Pan-Cancer TCGA and MSK-IMPACT cohorts. Multivariable Cox regression analyses stratified by cancer type defined adjusted hazard ratios (AHRs) for disease-specific survival (DSS), progression-free survival (PFS) and overall survival (OS). Results: Using TCGA we identified 32 mutated genes, and 15 copy number (CN) genes with frequency >= 4% in 9,104 patients across 28 cancers. On UVA, having a TP53-mutations or any mutation in the 31 genes (mut31) were associated with worse PFS (HR: 1.22, p < 0.0001 and HR: 1.1, p = 0.04, respectively) and DSS (HR: 1.38, p < 0.0001, and HR: 1.16, p = 0.03, respectively). CDKN2A, PTEN deletions, and MYC-amplifications were associated with PFS and DSS (p < 0.05 for all). On MVA, including TP53-mutations, mut31, CDKN2A-deletion, PTEN-deletion, and MYC-amplification, all five alterations were independently prognostic of poor PFS and DSS. Similar results were observed in an independent cohort from MSK-IMPACT (n = 7,051) where TP53 was associated with poor OS independent of mut31 and CN alterations in CDKN2A, PTEN, and MYC in primary tumors (p < 0.0001). Conclusions: TP53-mutations, CDKN2A-deletion, PTEN-deletion, and MYC-amplification are independent pan-cancer prognostic genomic alterations. Sign up for free Altmetric alerts about this article - Press release - Keywords - genomic alterations, TP53, TCGA, poor prognosis About Oncotarget Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. To learn more about Oncotarget, please visit and connect with us: SoundCloud - Facebook - Twitter - Instagram - YouTube - LinkedIn - Pinterest - Reddit - Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

    Analytical TechniquesCancer ResearchCell Science

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