Chromosomal copy number heterogeneity predicts survival rates across cancers.


Type
Article
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Authors
van Dijk, Erik 
El Makrini, Khalid 
Nijman, Lisanne E 
Abstract

Survival rates of cancer patients vary widely within and between malignancies. While genetic aberrations are at the root of all cancers, individual genomic features cannot explain these distinct disease outcomes. In contrast, intra-tumour heterogeneity (ITH) has the potential to elucidate pan-cancer survival rates and the biology that drives cancer prognosis. Unfortunately, a comprehensive and effective framework to measure ITH across cancers is missing. Here, we introduce a scalable measure of chromosomal copy number heterogeneity (CNH) that predicts patient survival across cancers. We show that the level of ITH can be derived from a single-sample copy number profile. Using gene-expression data and live cell imaging we demonstrate that ongoing chromosomal instability underlies the observed heterogeneity. Analysing 11,534 primary cancer samples from 37 different malignancies, we find that copy number heterogeneity can be accurately deduced and predicts cancer survival across tissues of origin and stages of disease. Our results provide a unifying molecular explanation for the different survival rates observed between cancer types.

Description

Funder: Medical Research Council


Funder: Cancer Research UK

Keywords
Humans, Neoplasms, Prognosis, Survival Rate, Risk Assessment, Gene Expression Profiling, Genomics, Gene Expression Regulation, Neoplastic, Genetic Heterogeneity, Mutation, Models, Genetic, Computer Simulation, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Child, Female, Male, Young Adult, DNA Copy Number Variations, Tumor Microenvironment, Datasets as Topic, Progression-Free Survival
Journal Title
Nature communications
Conference Name
Journal ISSN
2041-1723
Volume Title
12
Publisher