Comutation and exclusion analysis in human tumors: A tool for cancer biology studies and for rational selection of multitargeted therapeutic approaches
| العنوان: | Comutation and exclusion analysis in human tumors: A tool for cancer biology studies and for rational selection of multitargeted therapeutic approaches |
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| المؤلفون: | Elizabeth Martínez-Pérez, Miguel Angel Molina-Vila, Diego Javier Zea, Soledad Ochoa, Cristina Marino-Buslje |
| المصدر: | Human Mutation. 40:413-425 |
| بيانات النشر: | Hindawi Limited, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Otras Ciencias Biológicas, Quantitative Trait Loci, PAN-CANCER ANALYSIS, Computational biology, Biology, Mutually exclusive events, COMUTATION, MUTUAL EXCLUSIVITY, Ciencias Biológicas, 03 medical and health sciences, Neoplasms, Biomarkers, Tumor, Genetics, medicine, Humans, Gene Regulatory Networks, Molecular Targeted Therapy, Cancer biology, Genetics (clinical), Selection (genetic algorithm), 030304 developmental biology, Epigenomics, MULTITARGET THERAPY, 0303 health sciences, 030305 genetics & heredity, Chromosome Mapping, Computational Biology, Cancer, SOMATIC MUTATIONS, medicine.disease, Gene Expression Regulation, Neoplastic, Mutation, Disease Susceptibility, CIENCIAS NATURALES Y EXACTAS |
| الوصف: | Malignant tumors originate from somatic mutations and other genomic and epigenomic alterations, which lead to loss of control of the cellular circuitry. These alterations present patterns of co‐occurrence and mutual exclusivity that can influence prognosis and modify response to drugs, highlighting the need for multitargeted therapies. Studies in this area have generally focused in particular malignancies and considered whole genes instead of specific mutations, ignoring the fact that different alterations in the same gene can have widely different effects. Here, we present a comprehensive analysis of co‐dependencies of individual somatic mutations in the whole spectrum of human tumors. Combining multitesting with conditional and expected mutational probabilities, we have discovered rules governing the codependencies of driver and nondriver mutations. We also uncovered pairs and networks of comutations and exclusions, some of them restricted to certain cancer types and others widespread. These pairs and networks are not only of basic but also of clinical interest, and can be of help in the selection of multitargeted antitumor therapies. In this respect, recurrent driver comutations suggest combinations of drugs that might be effective in the clinical setting, while recurrent exclusions indicate combinations unlikely to be useful. Fil: Ochoa, Soledad. Fundación Instituto Leloir; Argentina Fil: Martinez Perez, Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Instituto Leloir; Argentina Fil: Zea, Diego Javier. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Instituto Leloir; Argentina Fil: Molina Vila, Miguel Angel. Hospital Universitario Quirón Dexeus; España Fil: Marino, Cristina Ester. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Instituto Leloir; Argentina |
| وصف الملف: | application/pdf |
| تدمد: | 1098-1004 1059-7794 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d2879c7a94d953d6dc8190b68f4f598eTest https://doi.org/10.1002/humu.23705Test |
| حقوق: | RESTRICTED |
| رقم الانضمام: | edsair.doi.dedup.....d2879c7a94d953d6dc8190b68f4f598e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10981004 10597794 |
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