Genomic Alterations Predictive of Poor Clinical Outcomes in Pan-cancer | Oncotarget
Channel: Oncotarget
Date: 04/10/2022

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. 
#openaccess #researchpaper #peerreview #cancer #research #oncologyresearch

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.

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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

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