Chromosome arm aneuploidies shape tumour evolution and drug response

Ankit Shukla, Thu H. M. Nguyen, Sarat B. Moka, Jonathan J. Ellis, John P. Grady, Harald Oey, Alexandre S. Cristino, Kum Kum Khanna, Dirk P. Kroese, Lutz Krause, Eloise Dray, J. Lynn Fink, Pascal H. G. Duijf*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)
5 Downloads (Pure)

Abstract

Chromosome arm aneuploidies (CAAs) are pervasive in cancers. However, how they affect cancer development, prognosis and treatment remains largely unknown. Here, we analyse CAA profiles of 23,427 tumours, identifying aspects of tumour evolution including probable orders in which CAAs occur and CAAs predicting tissue-specific metastasis. Both haematological and solid cancers initially gain chromosome arms, while only solid cancers subsequently preferentially lose multiple arms. 72 CAAs and 88 synergistically co-occurring CAA pairs multivariately predict good or poor survival for 58% of 6977 patients, with negligible impact of whole-genome doubling. Additionally, machine learning identifies 31 CAAs that robustly alter response to 56 chemotherapeutic drugs across cell lines representing 17 cancer types. We also uncover 1024 potential synthetic lethal pharmacogenomic interactions. Notably, in predicting drug response, CAAs substantially outperform mutations and focal deletions/amplifications combined. Thus, CAAs predict cancer prognosis, shape tumour evolution, metastasis and drug response, and may advance precision oncology.

Original languageEnglish
Article number449
Pages (from-to)1-14
Number of pages14
JournalNature Communications
Volume11
DOIs
Publication statusPublished - 2020
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2020. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Fingerprint

Dive into the research topics of 'Chromosome arm aneuploidies shape tumour evolution and drug response'. Together they form a unique fingerprint.

Cite this