Genetic Interaction-Based Biomarkers Identification for Drug Resistance and Sensitivity in Cancer Cells
Cancer cells generally harbor hundreds of alterations in the cancer genomes and act as crucial factors in the development and progression of cancer. Gene alterations in the cancer genome form genetic interactions, which affect the response of patients to drugs. We developed an algorithm that mines c...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-09-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253119301933 |
| _version_ | 1819045904400777216 |
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| author | Yue Han Chengyu Wang Qi Dong Tingting Chen Fan Yang Yaoyao Liu Bo Chen Zhangxiang Zhao Lishuang Qi Wenyuan Zhao Haihai Liang Zheng Guo Yunyan Gu |
| author_facet | Yue Han Chengyu Wang Qi Dong Tingting Chen Fan Yang Yaoyao Liu Bo Chen Zhangxiang Zhao Lishuang Qi Wenyuan Zhao Haihai Liang Zheng Guo Yunyan Gu |
| author_sort | Yue Han |
| collection | DOAJ |
| description | Cancer cells generally harbor hundreds of alterations in the cancer genomes and act as crucial factors in the development and progression of cancer. Gene alterations in the cancer genome form genetic interactions, which affect the response of patients to drugs. We developed an algorithm that mines copy number alteration and whole-exome mutation profiles from The Cancer Genome Atlas (TCGA), as well as functional screen data generated to identify potential genetic interactions for specific cancer types. As a result, 4,529 synthetic viability (SV) interactions and 10,637 synthetic lethality (SL) interactions were detected. The pharmacogenomic datasets revealed that SV interactions induced drug resistance in cancer cells and that SL interactions mediated drug sensitivity in cancer cells. Deletions of HDAC1 and DVL1, both of which participate in the Notch signaling pathway, had an SV effect in cancer cells, and deletion of DVL1 induced resistance to HDAC1 inhibitors in cancer cells. In addition, patients with low expression of both HDAC1 and DVL1 had poor prognosis. Finally, by integrating current reported genetic interactions from other studies, the Cancer Genetic Interaction database (CGIdb) (http://www.medsysbio.org/CGIdb) was constructed, providing a convenient retrieval for genetic interactions in cancer. Keywords: synthetic viability, synthetic lethality, drug resistance, drug sensitivity, biomarker |
| first_indexed | 2024-12-21T10:35:59Z |
| format | Article |
| id | doaj.art-49897a88cefd425b924be8c0bd603691 |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-21T10:35:59Z |
| publishDate | 2019-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-49897a88cefd425b924be8c0bd6036912022-12-21T19:07:04ZengElsevierMolecular Therapy: Nucleic Acids2162-25312019-09-0117688700Genetic Interaction-Based Biomarkers Identification for Drug Resistance and Sensitivity in Cancer CellsYue Han0Chengyu Wang1Qi Dong2Tingting Chen3Fan Yang4Yaoyao Liu5Bo Chen6Zhangxiang Zhao7Lishuang Qi8Wenyuan Zhao9Haihai Liang10Zheng Guo11Yunyan Gu12Department of Systems Biology, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150086, ChinaDepartment of Systems Biology, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150086, ChinaDepartment of Systems Biology, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150086, ChinaDepartment of Systems Biology, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150086, ChinaDepartment of Systems Biology, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150086, ChinaDepartment of Systems Biology, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150086, ChinaDepartment of Systems Biology, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150086, ChinaDepartment of Systems Biology, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150086, ChinaDepartment of Systems Biology, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150086, ChinaDepartment of Systems Biology, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150086, ChinaDepartment of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, ChinaDepartment of Systems Biology, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150086, China; Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Department of Bioinformatics, Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China; Corresponding author: Zheng Guo, Department of Systems Biology, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150086, China.Department of Systems Biology, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150086, China; Corresponding author: Yunyan Gu, Department of Systems Biology, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150086, China.Cancer cells generally harbor hundreds of alterations in the cancer genomes and act as crucial factors in the development and progression of cancer. Gene alterations in the cancer genome form genetic interactions, which affect the response of patients to drugs. We developed an algorithm that mines copy number alteration and whole-exome mutation profiles from The Cancer Genome Atlas (TCGA), as well as functional screen data generated to identify potential genetic interactions for specific cancer types. As a result, 4,529 synthetic viability (SV) interactions and 10,637 synthetic lethality (SL) interactions were detected. The pharmacogenomic datasets revealed that SV interactions induced drug resistance in cancer cells and that SL interactions mediated drug sensitivity in cancer cells. Deletions of HDAC1 and DVL1, both of which participate in the Notch signaling pathway, had an SV effect in cancer cells, and deletion of DVL1 induced resistance to HDAC1 inhibitors in cancer cells. In addition, patients with low expression of both HDAC1 and DVL1 had poor prognosis. Finally, by integrating current reported genetic interactions from other studies, the Cancer Genetic Interaction database (CGIdb) (http://www.medsysbio.org/CGIdb) was constructed, providing a convenient retrieval for genetic interactions in cancer. Keywords: synthetic viability, synthetic lethality, drug resistance, drug sensitivity, biomarkerhttp://www.sciencedirect.com/science/article/pii/S2162253119301933 |
| spellingShingle | Yue Han Chengyu Wang Qi Dong Tingting Chen Fan Yang Yaoyao Liu Bo Chen Zhangxiang Zhao Lishuang Qi Wenyuan Zhao Haihai Liang Zheng Guo Yunyan Gu Genetic Interaction-Based Biomarkers Identification for Drug Resistance and Sensitivity in Cancer Cells Molecular Therapy: Nucleic Acids |
| title | Genetic Interaction-Based Biomarkers Identification for Drug Resistance and Sensitivity in Cancer Cells |
| title_full | Genetic Interaction-Based Biomarkers Identification for Drug Resistance and Sensitivity in Cancer Cells |
| title_fullStr | Genetic Interaction-Based Biomarkers Identification for Drug Resistance and Sensitivity in Cancer Cells |
| title_full_unstemmed | Genetic Interaction-Based Biomarkers Identification for Drug Resistance and Sensitivity in Cancer Cells |
| title_short | Genetic Interaction-Based Biomarkers Identification for Drug Resistance and Sensitivity in Cancer Cells |
| title_sort | genetic interaction based biomarkers identification for drug resistance and sensitivity in cancer cells |
| url | http://www.sciencedirect.com/science/article/pii/S2162253119301933 |
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