Defining signatures of arm-wise copy number change and their associated drivers in kidney cancers

Benstead-Hume, Graeme, Wooller, Sarah, Downs, Jessica and Pearl, Frances (2019) Defining signatures of arm-wise copy number change and their associated drivers in kidney cancers. International Journal of Molecular Sciences, 20 (22). a5762. ISSN 1661-6596

[img] PDF (Defining signatures of arm-wise copy number change and their associated drivers in kidney cancers) - Published Version
Available under License Creative Commons Attribution.

Download (2MB)

Abstract

Using pan-cancer data from The Cancer Genome Atlas (TCGA), we investigated how patterns in copy number alterations in cancer cells vary both by tissue type and as a function of genetic alteration. We find that patterns in both chromosomal ploidy and individual arm copy number are dependent on tumour type. We highlight for example, the significant losses in chromosome arm 3p and the gain of ploidy in 5q in kidney clear cell renal cell carcinoma tissue samples. We find that specific gene mutations are associated with genome-wide copy number changes. Using
signatures derived from non-negative matrix factorisation (NMF), we also find gene mutations that are associated with particular patterns of ploidy change. Finally, utilising a set of machine learning classifiers, we successfully predicted the presence of mutated genes in a sample using arm-wise copy number patterns as features. This demonstrates that mutations in specific genes are correlated and may lead to specific patterns of ploidy loss and gain across chromosome arms. Using these same classifiers, we highlight which arms are most predictive of commonly mutated genes in kidney renal clear cell carcinoma (KIRC).

Item Type: Article
Schools and Departments: School of Life Sciences > Biochemistry
School of Life Sciences > Sussex Centre for Genome Damage and Stability
Subjects: Q Science
Q Science > QH Natural history > QH0301 Biology > QH0426 Genetics
Depositing User: Frances Pearl
Date Deposited: 08 Jan 2020 08:35
Last Modified: 08 Jan 2020 08:45
URI: http://sro.sussex.ac.uk/id/eprint/89223

View download statistics for this item

📧 Request an update
Project NameSussex Project NumberFunderFunder Ref
UnsetMR/N50189X/1Medical Research CouncilUnset