Targeted sequencing reveals genetic variants associated with sensitivity of 79 human cancer xenografts to anticancer drugs
| Autor: | Yasushi Sasaki, Yasuyuki Ohnishi, Hiroshi Ohnishi, Hitoshi Zembutsu, Chihiro Udagawa, Takashi Tokino, Hiroshi Suemizu |
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| Rok vydání: | 2017 |
| Předmět: |
Cancer Research
Vincristine Cyclophosphamide 030226 pharmacology & pharmacy 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Immunology and Microbiology (miscellaneous) medicine cytotoxic anticancer drugs xenograft Cisplatin next generation sequencing pharmacogenomics business.industry Nimustine Cancer General Medicine Articles medicine.disease Molecular medicine Molecular biology Vinblastine chemistry 030220 oncology & carcinogenesis Pharmacogenomics Cancer research biomarker business medicine.drug |
| Zdroj: | Experimental and Therapeutic Medicine |
| ISSN: | 1792-0981 |
| Popis: | Although there has been progress moving from a 'one-size-fits-all' cytotoxic approach to personalized molecular medicine, the majority of patients with cancer receive chemotherapy using cytotoxic anticancer drugs. The sequencing analysis of 409 genes associated with cancer was conducted in the present study using 59 DNA sequences extracted from human cancer xenografts implanted into nude mice, of which sensitivity to 9 cytotoxic anticancer drugs [5-fluorouracil, nimustine, adriamycin, cyclophosphamide, cisplatin, mitomycin C (MMC), methotrexate, vincristine (VCR), and vinblastine] was examined. The present study investigated the association between the sensitivities of the xenografts to the 9 anticancer drugs and the frequency of single nucleotide variants (SNV). The correlation between the expression level of the genes and sensitivities to the 9 drugs in the above xenografts was also estimated. In the screening study using 59 xenografts, 3 SNVs (rs1805321, rs62456182 in PMS1 Homolog 2, Mismatch Repair System Component and rs13382825 in LDL Receptor Related Protein 1B), were associated with sensitivity to VCR and MMC, respectively (P |
| Databáze: | OpenAIRE |
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