Chromosome arm aneuploidies shape tumour evolution and drug response
By A. Shukla, T. Nguyen, S. Moka, J. Ellis, J. Grady, H. Oey, A. Cristino, Kum Khanna, Dirk P. Kroese, L. Krause and 3 more. 2020
96 citations recorded by the source corpus.
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.
Subfields: Cancer Research, Cell Biology, Molecular Biology
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In Molecular Biology
- Syuzo Kaneko
- Masaaki Komatsu
- Ken Asada
- Ken Takasawa
- Amina Bolatkan
- Jun Sese
- Ryuji Hamamoto
- Yusuke Nakamura
Citations in the corpus
- Application of Artificial Intelligence Technology in Oncology: Towards the Establishment of Precision Medicine (2020, methodology): “analyzed the chromos e arm neuploidy (CAA) profiles of 23,427 tumors to identify the aspects of tumor ev lution, including the order in which CAAs can occur and the CAAs that can predict tissue-specific metastases [115].”