A map of human cancer signaling
Abstract We conducted a comprehensive analysis of a manually curated human signaling network containing 1634 nodes and 5089 signaling regulatory relations by integrating cancer‐associated genetically and epigenetically altered genes. We find that cancer mutated genes are enriched in positive signali...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2007-12-01
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| Series: | Molecular Systems Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/msb4100200 |
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| _version_ | 1849225791109332992 |
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| author | Qinghua Cui Yun Ma Maria Jaramillo Hamza Bari Arif Awan Song Yang Simo Zhang Lixue Liu Meng Lu Maureen O'Connor‐McCourt Enrico O Purisima Edwin Wang |
| author_facet | Qinghua Cui Yun Ma Maria Jaramillo Hamza Bari Arif Awan Song Yang Simo Zhang Lixue Liu Meng Lu Maureen O'Connor‐McCourt Enrico O Purisima Edwin Wang |
| author_sort | Qinghua Cui |
| collection | DOAJ |
| description | Abstract We conducted a comprehensive analysis of a manually curated human signaling network containing 1634 nodes and 5089 signaling regulatory relations by integrating cancer‐associated genetically and epigenetically altered genes. We find that cancer mutated genes are enriched in positive signaling regulatory loops, whereas the cancer‐associated methylated genes are enriched in negative signaling regulatory loops. We further characterized an overall picture of the cancer‐signaling architectural and functional organization. From the network, we extracted an oncogene‐signaling map, which contains 326 nodes, 892 links and the interconnections of mutated and methylated genes. The map can be decomposed into 12 topological regions or oncogene‐signaling blocks, including a few ‘oncogene‐signaling‐dependent blocks’ in which frequently used oncogene‐signaling events are enriched. One such block, in which the genes are highly mutated and methylated, appears in most tumors and thus plays a central role in cancer signaling. Functional collaborations between two oncogene‐signaling‐dependent blocks occur in most tumors, although breast and lung tumors exhibit more complex collaborative patterns between multiple blocks than other cancer types. Benchmarking two data sets derived from systematic screening of mutations in tumors further reinforced our findings that, although the mutations are tremendously diverse and complex at the gene level, clear patterns of oncogene‐signaling collaborations emerge recurrently at the network level. Finally, the mutated genes in the network could be used to discover novel cancer‐associated genes and biomarkers. |
| format | Article |
| id | doaj-art-bb82f4b756454fc0b84d61d76e1c433d |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2007-12-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-bb82f4b756454fc0b84d61d76e1c433d2025-08-24T12:02:08ZengSpringer NatureMolecular Systems Biology1744-42922007-12-013111310.1038/msb4100200A map of human cancer signalingQinghua Cui0Yun Ma1Maria Jaramillo2Hamza Bari3Arif Awan4Song Yang5Simo Zhang6Lixue Liu7Meng Lu8Maureen O'Connor‐McCourt9Enrico O Purisima10Edwin Wang11Computational Chemistry and Biology Group, Biotechnology Research Institute, National Research Council CanadaDepartment of Biology, Tianjin Normal UniversityReceptor, Signaling and Proteomics Group, Biotechnology Research Institute, National Research Council CanadaComputational Chemistry and Biology Group, Biotechnology Research Institute, National Research Council CanadaComputational Chemistry and Biology Group, Biotechnology Research Institute, National Research Council CanadaSchool of Chemical Engineering, Tianjin UniversityDepartment of Biology, Tianjin Normal UniversityDepartment of Biology, Tianjin Normal UniversityDepartment of Biology, Tianjin Normal UniversityReceptor, Signaling and Proteomics Group, Biotechnology Research Institute, National Research Council CanadaComputational Chemistry and Biology Group, Biotechnology Research Institute, National Research Council CanadaComputational Chemistry and Biology Group, Biotechnology Research Institute, National Research Council CanadaAbstract We conducted a comprehensive analysis of a manually curated human signaling network containing 1634 nodes and 5089 signaling regulatory relations by integrating cancer‐associated genetically and epigenetically altered genes. We find that cancer mutated genes are enriched in positive signaling regulatory loops, whereas the cancer‐associated methylated genes are enriched in negative signaling regulatory loops. We further characterized an overall picture of the cancer‐signaling architectural and functional organization. From the network, we extracted an oncogene‐signaling map, which contains 326 nodes, 892 links and the interconnections of mutated and methylated genes. The map can be decomposed into 12 topological regions or oncogene‐signaling blocks, including a few ‘oncogene‐signaling‐dependent blocks’ in which frequently used oncogene‐signaling events are enriched. One such block, in which the genes are highly mutated and methylated, appears in most tumors and thus plays a central role in cancer signaling. Functional collaborations between two oncogene‐signaling‐dependent blocks occur in most tumors, although breast and lung tumors exhibit more complex collaborative patterns between multiple blocks than other cancer types. Benchmarking two data sets derived from systematic screening of mutations in tumors further reinforced our findings that, although the mutations are tremendously diverse and complex at the gene level, clear patterns of oncogene‐signaling collaborations emerge recurrently at the network level. Finally, the mutated genes in the network could be used to discover novel cancer‐associated genes and biomarkers.https://doi.org/10.1038/msb4100200cancer signalingcancer‐signaling mapDNA methylationgene mutationoncogenesignaling dependencesignaling network |
| spellingShingle | Qinghua Cui Yun Ma Maria Jaramillo Hamza Bari Arif Awan Song Yang Simo Zhang Lixue Liu Meng Lu Maureen O'Connor‐McCourt Enrico O Purisima Edwin Wang A map of human cancer signaling Molecular Systems Biology cancer signaling cancer‐signaling map DNA methylation gene mutation oncogenesignaling dependence signaling network |
| title | A map of human cancer signaling |
| title_full | A map of human cancer signaling |
| title_fullStr | A map of human cancer signaling |
| title_full_unstemmed | A map of human cancer signaling |
| title_short | A map of human cancer signaling |
| title_sort | map of human cancer signaling |
| topic | cancer signaling cancer‐signaling map DNA methylation gene mutation oncogenesignaling dependence signaling network |
| url | https://doi.org/10.1038/msb4100200 |
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