Chromosome arm aneuploidies shape tumour evolution and drug response
| Autor: | Harald Oey, J. Lynn Fink, Ankit Shukla, Kum Kum Khanna, Eloise Dray, Jonathan Ellis, Alexandre S. Cristino, Thu H.M. Nguyen, John P. Grady, Dirk P. Kroese, Lutz Krause, Pascal H.G. Duijf, Sarat B. Moka |
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| Přispěvatelé: | Shukla, Ankit, Nguyen, Thu HM, Moka, Sarat B, Ellis, Jonathan J, Grady, John P, Oey, Harald, Cristino, Alexandre S, Khanna, Kum Kum, Kroese, Dirk P, Krause, Lutz, Dray, Eloise, Fink, J Lynn, Duijf, Pascal HG |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Mutation rate General Physics and Astronomy Aneuploidy Kaplan-Meier Estimate Drug resistance Metastasis Machine Learning 0302 clinical medicine Mutation Rate Neoplasms Chromosomes Human Medicine chromosome lcsh:Science Multidisciplinary drug Prognosis Cancer therapeutic resistance machine learning 030220 oncology & carcinogenesis Chromosome Arm Systems biology tumor Science Models Biological Article General Biochemistry Genetics and Molecular Biology developmental biology 03 medical and health sciences Cell Line Tumor evolution mental disorders Humans Chemotherapy cancer cardiovascular diseases Stochastic Processes business.industry Chromosome Cancer nutritional and metabolic diseases General Chemistry medicine.disease 030104 developmental biology Drug Resistance Neoplasm Pharmacogenomics Cancer research lcsh:Q cell component business |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-14 (2020) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. Chromosome arm-level aneuploidies (CAAs) are frequently observed in cancer. Here, the authors analyse CAA landscapes across different tumour types, relating these chromosome arm gains and losses to tumour evolution, metastasis, patient survival and response to a range of anti-cancer therapies. |
| Databáze: | OpenAIRE |
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