Abstract
AbstractChromosome 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.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
Reference57 articles.
1. Hanahan, D. & Weinberg, R. A. Hallmarks of cancer: the next generation. Cell 144, 646–674 (2011).
2. Negrini, S., Gorgoulis, V. G. & Halazonetis, T. D. Genomic instability—an evolving hallmark of cancer. Nat. Rev. Mol. Cell Biol. 11, 220–228 (2010).
3. Burrell, R. A., McGranahan, N., Bartek, J. & Swanton, C. The causes and consequences of genetic heterogeneity in cancer evolution. Nature 501, 338–345 (2013).
4. Duijf, P. H., Schultz, N. & Benezra, R. Cancer cells preferentially lose small chromosomes. Int J. Cancer 132, 2316–2326 (2013).
5. Tanaka, K. & Hirota, T. Chromosomal instability: a common feature and a therapeutic target of cancer. Biochim Biophys. Acta 1866, 64–75 (2016).
Cited by
81 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献