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

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October 4, 2022

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 - https://doi.org/10.18632/oncotarget.28276 Correspondence to - Mohammed Alshalalfa - mohamed.alshalalfa@gmail.com 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 - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28276 Press release - https://www.oncotarget.com/news/pr/oncotarget-genomic-alterations-predictive-of-poor-clinical-outcomes-in-pan-cancer/ 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 https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

Analytical TechniquesCancer ResearchCell Science

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