دورية أكاديمية
Copy number aberrations drive kinase rewiring, leading to genetic vulnerabilities in cancer
| العنوان: | Copy number aberrations drive kinase rewiring, leading to genetic vulnerabilities in cancer |
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| المؤلفون: | Memon, Danish, Gill, Michael B., Papachristou, Evangelia K., Ochoa, David, D’Santos, Clive S., Miller, Martin L., Beltrao, Pedro, id_orcid:0 000-0002-2724-7703 |
| المصدر: | Cell Reports, 35 (7) |
| بيانات النشر: | Cell Press |
| سنة النشر: | 2021 |
| المجموعة: | ETH Zürich Research Collection |
| مصطلحات موضوعية: | cancer, copy number aberrations, genetic associations, phospho-regulation, kinase addiction, precision medicine |
| الوصف: | Somatic DNA copy number variations (CNVs) are prevalent in cancer and can drive cancer progression, albeit with often uncharacterized roles in altering cell signaling states. Here, we integrate genomic and proteomic data for 5,598 tumor samples to identify CNVs leading to aberrant signal transduction. The resulting associations recapitulate known kinase-substrate relationships, and further network analysis prioritizes likely causal genes. Of the 303 significant associations we identify from the pan-tumor analysis, 43% are replicated in cancer cell lines, including 44 robust gene-phosphosite associations identified across multiple tumor types. Several predicted regulators of hippo signaling are experimentally validated. Using RNAi, CRISPR, and drug screening data, we find evidence of kinase addiction in cancer cell lines, identifying inhibitors for targeting of kinase-dependent cell lines. We propose copy number status of genes as a useful predictor of differential impact of kinase inhibition, a strategy that may be of use in the future for anticancer therapies. ; ISSN:2666-3864 ; ISSN:2211-1247 |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/application/pdf |
| اللغة: | English |
| العلاقة: | http://hdl.handle.net/20.500.11850/531935Test |
| DOI: | 10.3929/ethz-b-000531935 |
| الإتاحة: | https://doi.org/20.500.11850/531935Test https://doi.org/10.3929/ethz-b-000531935Test https://doi.org/10.1016/j.celrep.2021.109155Test https://hdl.handle.net/20.500.11850/531935Test |
| حقوق: | info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by/4.0Test/ ; Creative Commons Attribution 4.0 International |
| رقم الانضمام: | edsbas.606CC7B5 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3929/ethz-b-000531935 |
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