Pharmacogenomic Profiling of Cisplatin-Resistant and -Sensitive Human Osteosarcoma Cell Lines by Multimodal Targeted Next Generation Sequencing
Cisplatin (CDDP) is a drug for high-grade osteosarcoma (HGOS) treatment. Several germline pharmacogenetic studies have revealed associations between single nucleotide polymorphisms (SNPs) and CDDP-based therapy response or CDDP-related toxicity in patients with HGOS. Whether these variants could pla...
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2022-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/19/11787 |
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| author | Claudia Maria Hattinger Chiara Casotti Maria Pia Patrizio Silvia Luppi Leonardo Fantoni Katia Scotlandi Toni Ibrahim Massimo Serra |
| author_facet | Claudia Maria Hattinger Chiara Casotti Maria Pia Patrizio Silvia Luppi Leonardo Fantoni Katia Scotlandi Toni Ibrahim Massimo Serra |
| author_sort | Claudia Maria Hattinger |
| collection | DOAJ |
| description | Cisplatin (CDDP) is a drug for high-grade osteosarcoma (HGOS) treatment. Several germline pharmacogenetic studies have revealed associations between single nucleotide polymorphisms (SNPs) and CDDP-based therapy response or CDDP-related toxicity in patients with HGOS. Whether these variants could play a biological role in HGOS cells has not been studied so far. The aim of this study was to explore 28 SNPs of 14 genes in 6 CDDP-resistant and 12 drug-sensitive human HGOS cell lines. An innovative multimodal targeted next generation sequencing (mmNGS) approach with custom primers designed for the most commonly reported SNPs of genes belonging to DNA repair, CDDP transport or detoxification, or associated with CDPP-related toxicity was applied. The mmNGS approach was validated by TaqMan genotyping assays and emerged to be an innovative, reliable tool to detect genetic polymorphisms at both the DNA and RNA level. Allele changes in three SNPs (<i>ERCC2</i> rs13181 and rs1799793, <i>ERCC1</i> rs11615) were identified on both DNA and RNA derived libraries in association with CDDP resistance. A change of the <i>GSTP1</i> rs1695 polymorphism from AA to AG genotype was observed in the RNA of all six CDDP-resistant variants. These SNPs emerged to be causally associated with CDDP resistance in HGOS cells. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:37:35Z |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b1a39508e9114e5eb1e900ab941b038d2023-11-23T20:39:17ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123191178710.3390/ijms231911787Pharmacogenomic Profiling of Cisplatin-Resistant and -Sensitive Human Osteosarcoma Cell Lines by Multimodal Targeted Next Generation SequencingClaudia Maria Hattinger0Chiara Casotti1Maria Pia Patrizio2Silvia Luppi3Leonardo Fantoni4Katia Scotlandi5Toni Ibrahim6Massimo Serra7Osteoncology, Bone and Soft Tissue Sarcomas and Innovative Therapies, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, ItalyOsteoncology, Bone and Soft Tissue Sarcomas and Innovative Therapies, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, ItalyLaboratory of Experimental Oncology, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, ItalyLaboratory of Experimental Oncology, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, ItalyOsteoncology, Bone and Soft Tissue Sarcomas and Innovative Therapies, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, ItalyLaboratory of Experimental Oncology, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, ItalyOsteoncology, Bone and Soft Tissue Sarcomas and Innovative Therapies, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, ItalyOsteoncology, Bone and Soft Tissue Sarcomas and Innovative Therapies, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, ItalyCisplatin (CDDP) is a drug for high-grade osteosarcoma (HGOS) treatment. Several germline pharmacogenetic studies have revealed associations between single nucleotide polymorphisms (SNPs) and CDDP-based therapy response or CDDP-related toxicity in patients with HGOS. Whether these variants could play a biological role in HGOS cells has not been studied so far. The aim of this study was to explore 28 SNPs of 14 genes in 6 CDDP-resistant and 12 drug-sensitive human HGOS cell lines. An innovative multimodal targeted next generation sequencing (mmNGS) approach with custom primers designed for the most commonly reported SNPs of genes belonging to DNA repair, CDDP transport or detoxification, or associated with CDPP-related toxicity was applied. The mmNGS approach was validated by TaqMan genotyping assays and emerged to be an innovative, reliable tool to detect genetic polymorphisms at both the DNA and RNA level. Allele changes in three SNPs (<i>ERCC2</i> rs13181 and rs1799793, <i>ERCC1</i> rs11615) were identified on both DNA and RNA derived libraries in association with CDDP resistance. A change of the <i>GSTP1</i> rs1695 polymorphism from AA to AG genotype was observed in the RNA of all six CDDP-resistant variants. These SNPs emerged to be causally associated with CDDP resistance in HGOS cells.https://www.mdpi.com/1422-0067/23/19/11787osteosarcomanext generation sequencingcisplatin resistancesingle nucleotide polymorphismpharmacogenomics |
| spellingShingle | Claudia Maria Hattinger Chiara Casotti Maria Pia Patrizio Silvia Luppi Leonardo Fantoni Katia Scotlandi Toni Ibrahim Massimo Serra Pharmacogenomic Profiling of Cisplatin-Resistant and -Sensitive Human Osteosarcoma Cell Lines by Multimodal Targeted Next Generation Sequencing International Journal of Molecular Sciences osteosarcoma next generation sequencing cisplatin resistance single nucleotide polymorphism pharmacogenomics |
| title | Pharmacogenomic Profiling of Cisplatin-Resistant and -Sensitive Human Osteosarcoma Cell Lines by Multimodal Targeted Next Generation Sequencing |
| title_full | Pharmacogenomic Profiling of Cisplatin-Resistant and -Sensitive Human Osteosarcoma Cell Lines by Multimodal Targeted Next Generation Sequencing |
| title_fullStr | Pharmacogenomic Profiling of Cisplatin-Resistant and -Sensitive Human Osteosarcoma Cell Lines by Multimodal Targeted Next Generation Sequencing |
| title_full_unstemmed | Pharmacogenomic Profiling of Cisplatin-Resistant and -Sensitive Human Osteosarcoma Cell Lines by Multimodal Targeted Next Generation Sequencing |
| title_short | Pharmacogenomic Profiling of Cisplatin-Resistant and -Sensitive Human Osteosarcoma Cell Lines by Multimodal Targeted Next Generation Sequencing |
| title_sort | pharmacogenomic profiling of cisplatin resistant and sensitive human osteosarcoma cell lines by multimodal targeted next generation sequencing |
| topic | osteosarcoma next generation sequencing cisplatin resistance single nucleotide polymorphism pharmacogenomics |
| url | https://www.mdpi.com/1422-0067/23/19/11787 |
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