دورية أكاديمية
Patient-specific cancer genes contribute to recurrently perturbed pathways and establish therapeutic vulnerabilities in esophageal adenocarcinoma
| العنوان: | Patient-specific cancer genes contribute to recurrently perturbed pathways and establish therapeutic vulnerabilities in esophageal adenocarcinoma |
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| المؤلفون: | Mourikis T. P., Benedetti L., Foxall E., Temelkovski D., Nulsen J., Perner J., Cereda M., Lagergren J., Howell M., Yau C., Fitzgerald R. C., Scaffidi P., Noorani A., Edwards P. A. W., Elliott R. F., Grehan N., Nutzinger B., Hughes C., Fidziukiewicz E., Bornschein J., MacRae S., Crawte J., Northrop A., Contino G., Li X., de la Rue R., Katz-Summercorn A., Abbas S., Loureda D., O'Donovan M., Miremadi A., Malhotra S., Tripathi M., Tavare S., Lynch A. G., Eldridge M., Secrier M., Bower L., Devonshire G., Jammula S., Davies J., Crichton C., Carroll N., Safranek P., Hindmarsh A., Sujendran V., Hayes S. J., Ang Y., Sharrocks A., Preston S. R., Oakes S., Bagwan I., Save V., Skipworth R. J. E., Hupp T. R., Robert O'Neill J., Tucker O., Beggs A., Taniere P., Puig S., Underwood T. J., Walker R. C., Grace B. L., Barr H., Shepherd N., Old O., Gossage J., Davies A., Chang F., Zylstra J., Mahadeva U., Goh V., Sanders G., Berrisford R., Harden C., Lewis M., Cheong E., Kumar B., Parsons S. L., Soomro I., Kaye P., Saunders J., Lovat L., Haidry R., Igali L., Scott M., Sothi S., Suortamo S., Lishman S., Hanna G. B., Peters C. J., Moorthy K., Grabowska A., Turkington R., McManus D., Khoo D., Fickling W., Ciccarelli F. D. |
| المساهمون: | T.P. Mouriki, L. Benedetti, E. Foxall, D. Temelkovski, J. Nulsen, J. Perner, M. Cereda, J. Lagergren, M. Howell, C. Yau, R.C. Fitzgerald, P. Scaffidi, A. Noorani, P.A.W. Edward, R.F. Elliott, N. Grehan, B. Nutzinger, C. Hughe, E. Fidziukiewicz, J. Bornschein, S. Macrae, J. Crawte, A. Northrop, G. Contino, X. Li, R. de la Rue, A. Katz-Summercorn, S. Abba, D. Loureda, M. O'Donovan, A. Miremadi, S. Malhotra, M. Tripathi, S. Tavare, A.G. Lynch, M. Eldridge, M. Secrier, L. Bower, G. Devonshire, S. Jammula, J. Davie, C. Crichton, N. Carroll, P. Safranek, A. Hindmarsh, V. Sujendran, S.J. Haye, Y. Ang, A. Sharrock, S.R. Preston, S. Oake, I. Bagwan, V. Save, R.J.E. Skipworth, T.R. Hupp, J. Robert O'Neill, O. Tucker, A. Begg, P. Taniere, S. Puig, T.J. Underwood, R.C. Walker, B.L. Grace, H. Barr, N. Shepherd, O. Old, J. Gossage, A. Davie, F. Chang, J. Zylstra, U. Mahadeva, V. Goh, G. Sander, R. Berrisford, C. Harden, M. Lewi, E. Cheong, B. Kumar, S.L. Parson, I. Soomro, P. Kaye, J. Saunder, L. Lovat, R. Haidry, L. Igali, M. Scott, S. Sothi, S. Suortamo, S. Lishman, G.B. Hanna, C.J. Peter, K. Moorthy, A. Grabowska, R. Turkington, D. Mcmanu, D. Khoo, W. Fickling, F.D. Ciccarelli |
| بيانات النشر: | Nature Publishing Group |
| سنة النشر: | 2019 |
| المجموعة: | The University of Milan: Archivio Istituzionale della Ricerca (AIR) |
| مصطلحات موضوعية: | Adenocarcinoma, Antineoplastic Agent, Biomarkers, Tumor, Computational Biology, Datasets as Topic, Disease Progression, Esophageal Neoplasm, Gene Dosage, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Genomic Instability, Human, Machine Learning, Models, Genetic, Multigene Family, Mutation Rate, Polymorphism, Single Nucleotide, Precision Medicine, Settore BIO/11 - Biologia Molecolare, Settore MED/06 - Oncologia Medica |
| الوصف: | The identification of cancer-promoting genetic alterations is challenging particularly in highly unstable and heterogeneous cancers, such as esophageal adenocarcinoma (EAC). Here we describe a machine learning algorithm to identify cancer genes in individual patients considering all types of damaging alterations simultaneously. Analysing 261 EACs from the OCCAMS Consortium, we discover helpergenes that, alongside well-known drivers, promote cancer. We confirm the robustness of our approach in 107 additional EACs. Unlike recurrent alterations of known drivers, these cancer helpergenes are rare or patient-specific. However, they converge towards perturbations of well-known cancer processes. Recurrence of thesame process perturbations, rather than individual genes, divides EACs into six clusters differing in their molecular and clinical features. Experimentally mimicking the alterations of predicted helpergenes in cancer and pre-cancer cells validates their contribution to disease progression, while reverting their alterations reveals EAC acquired dependencies that can be exploited in therapy. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/31308377; info:eu-repo/semantics/altIdentifier/wos/WOS:000475469200005; volume:10; issue:1; firstpage:1; lastpage:17; numberofpages:17; journal:NATURE COMMUNICATIONS; http://hdl.handle.net/2434/898565Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85069459995 |
| DOI: | 10.1038/s41467-019-10898-3 |
| الإتاحة: | https://doi.org/10.1038/s41467-019-10898-3Test http://hdl.handle.net/2434/898565Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.11BEFC6D |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-019-10898-3 |
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