Language

English

Publication Date

7-2-2025

Journal

Nature Communications

DOI

10.1038/s41467-025-61063-y

PMID

40603285

PMCID

PMC12222647

PubMedCentral® Posted Date

7-2-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Chromosome instability leading to aneuploidy and accumulation of copy number gains or losses is a hallmark of cancer. Copy number alteration (CNA) signatures are increasingly used for cancer risk stratification, but size thresholds for defining CNAs across cancers are variable and the biological and clinical implications of CNA size heterogeneity and co-occurrence are incompletely understood. Here we analyze CNA and clinical data from 691 meningiomas and 10,383 tumors from The Cancer Genome Atlas to develop cancer- and chromosome-specific size-dependent CNA and CNA co-occurrence models to predict tumor control and overall survival. Our results shed light on technical considerations for biomarker development and reveal prognostic CNAs with optimized size thresholds and co-occurrence patterns that refine risk stratification across a diversity of cancer types. These data suggest that consideration of CNA size, focality, number, and co-occurrence can be used to identify biomarkers of aggressive tumor behavior that may be useful for individualized risk stratification.

Keywords

Humans, DNA Copy Number Variations, Neoplasms, Risk Assessment, Prognosis, Biomarkers, Tumor, Meningioma, Female, Cancer genomics, Tumour biomarkers, CNS cancer

Published Open-Access

yes

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.