Driver mutations in GNAQ and GNA11 genes as potential targets for precision immunotherapy in uveal melanoma patients
Uveal melanoma (UM) is the most common ocular malignancy in adults. Nearly 95% of UM patients carry the mutually exclusive mutations in the homologous genes GNAQ (amino acid change Q209L/Q209P) and GNA11 (aminoacid change Q209L). UM is located in an immunosuppressed organ and does not suffer immunoe...
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Taylor & Francis Group
2023-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2261278 |
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| author | Sandra García-Mulero Roberto Fornelino Marco Punta Stefano Lise Mar Varela Luis P. del Carpio Rafael Moreno Marcel Costa-García Dietmar Rieder Zlatko Trajanoski Alena Gros Ramón Alemany Josep María Piulats Rebeca Sanz-Pamplona |
| author_facet | Sandra García-Mulero Roberto Fornelino Marco Punta Stefano Lise Mar Varela Luis P. del Carpio Rafael Moreno Marcel Costa-García Dietmar Rieder Zlatko Trajanoski Alena Gros Ramón Alemany Josep María Piulats Rebeca Sanz-Pamplona |
| author_sort | Sandra García-Mulero |
| collection | DOAJ |
| description | Uveal melanoma (UM) is the most common ocular malignancy in adults. Nearly 95% of UM patients carry the mutually exclusive mutations in the homologous genes GNAQ (amino acid change Q209L/Q209P) and GNA11 (aminoacid change Q209L). UM is located in an immunosuppressed organ and does not suffer immunoediting. Therefore, we hypothesize that driver mutations in GNAQ/11 genes could be recognized by the immune system. Genomic and transcriptomic data from primary uveal tumors were collected from the TCGA-UM dataset (n = 80) and used to assess the immunogenic potential for GNAQ/GNA11 Q209L/Q209P mutations using a variety of tools and HLA type information. All prediction tools showed stronger GNAQ/11 Q209L binding to HLA than GNAQ/11 Q209P. The immunogenicity analysis revealed that Q209L is likely to be presented by more than 73% of individuals in 1000 G databases whereas Q209P is only predicted to be presented in 24% of individuals. GNAQ/11 Q209L showed a higher likelihood to be presented by HLA-I molecules than almost all driver mutations analyzed. Finally, samples carrying Q209L had a higher immune-reactive phenotype. Regarding cancer risk, seven HLA genotypes with low Q209L affinity show higher frequency in uveal melanoma patients than in the general population. However, no clear association was found between any HLA genotype and survival. Results suggest a high potential immunogenicity of the GNAQ/11 Q209L variant that could allow the generation of novel therapeutic tools to treat UM like neoantigen vaccinations. |
| format | Article |
| id | doaj-art-623ba2cd7fe440f08b80ee759bb43d1a |
| institution | OA Journals |
| issn | 2162-402X |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-623ba2cd7fe440f08b80ee759bb43d1a2025-08-20T02:01:30ZengTaylor & Francis GroupOncoImmunology2162-402X2023-12-0112110.1080/2162402X.2023.2261278Driver mutations in GNAQ and GNA11 genes as potential targets for precision immunotherapy in uveal melanoma patientsSandra García-Mulero0Roberto Fornelino1Marco Punta2Stefano Lise3Mar Varela4Luis P. del Carpio5Rafael Moreno6Marcel Costa-García7Dietmar Rieder8Zlatko Trajanoski9Alena Gros10Ramón Alemany11Josep María Piulats12Rebeca Sanz-Pamplona13Unit of Biomarkers and Susceptibility, Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL) and CIBERESP, Barcelona, SpainUnit of Biomarkers and Susceptibility, Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL) and CIBERESP, Barcelona, SpainBioinformatics Core, Centre for Evolution and Cancer, The Institute of Cancer Research, London, UKBioinformatics Core, Centre for Evolution and Cancer, The Institute of Cancer Research, London, UKDepartment of Pathology, Bellvitge University Hospital, Barcelona, SpainProcure Program, Catalan Institute of Oncology (ICO), Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, SpainProcure Program, Catalan Institute of Oncology (ICO), Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, SpainProcure Program, Catalan Institute of Oncology (ICO), Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, SpainInstitute of Bioinformatics, Biocenter, Medical University of Innsbruck, Innsbruck, AustriaInstitute of Bioinformatics, Biocenter, Medical University of Innsbruck, Innsbruck, AustriaTumor Immunology and Immunotherapy, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, SpainProcure Program, Catalan Institute of Oncology (ICO), Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, SpainDepartment of Medical Oncology, ICO, IDIBELL and CIBERONC, Barcelona, SpainUnit of Biomarkers and Susceptibility, Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL) and CIBERESP, Barcelona, SpainUveal melanoma (UM) is the most common ocular malignancy in adults. Nearly 95% of UM patients carry the mutually exclusive mutations in the homologous genes GNAQ (amino acid change Q209L/Q209P) and GNA11 (aminoacid change Q209L). UM is located in an immunosuppressed organ and does not suffer immunoediting. Therefore, we hypothesize that driver mutations in GNAQ/11 genes could be recognized by the immune system. Genomic and transcriptomic data from primary uveal tumors were collected from the TCGA-UM dataset (n = 80) and used to assess the immunogenic potential for GNAQ/GNA11 Q209L/Q209P mutations using a variety of tools and HLA type information. All prediction tools showed stronger GNAQ/11 Q209L binding to HLA than GNAQ/11 Q209P. The immunogenicity analysis revealed that Q209L is likely to be presented by more than 73% of individuals in 1000 G databases whereas Q209P is only predicted to be presented in 24% of individuals. GNAQ/11 Q209L showed a higher likelihood to be presented by HLA-I molecules than almost all driver mutations analyzed. Finally, samples carrying Q209L had a higher immune-reactive phenotype. Regarding cancer risk, seven HLA genotypes with low Q209L affinity show higher frequency in uveal melanoma patients than in the general population. However, no clear association was found between any HLA genotype and survival. Results suggest a high potential immunogenicity of the GNAQ/11 Q209L variant that could allow the generation of novel therapeutic tools to treat UM like neoantigen vaccinations.https://www.tandfonline.com/doi/10.1080/2162402X.2023.2261278GNA11GNAQHLAimmunotherapyneoantigenuveal melanoma |
| spellingShingle | Sandra García-Mulero Roberto Fornelino Marco Punta Stefano Lise Mar Varela Luis P. del Carpio Rafael Moreno Marcel Costa-García Dietmar Rieder Zlatko Trajanoski Alena Gros Ramón Alemany Josep María Piulats Rebeca Sanz-Pamplona Driver mutations in GNAQ and GNA11 genes as potential targets for precision immunotherapy in uveal melanoma patients OncoImmunology GNA11 GNAQ HLA immunotherapy neoantigen uveal melanoma |
| title | Driver mutations in GNAQ and GNA11 genes as potential targets for precision immunotherapy in uveal melanoma patients |
| title_full | Driver mutations in GNAQ and GNA11 genes as potential targets for precision immunotherapy in uveal melanoma patients |
| title_fullStr | Driver mutations in GNAQ and GNA11 genes as potential targets for precision immunotherapy in uveal melanoma patients |
| title_full_unstemmed | Driver mutations in GNAQ and GNA11 genes as potential targets for precision immunotherapy in uveal melanoma patients |
| title_short | Driver mutations in GNAQ and GNA11 genes as potential targets for precision immunotherapy in uveal melanoma patients |
| title_sort | driver mutations in gnaq and gna11 genes as potential targets for precision immunotherapy in uveal melanoma patients |
| topic | GNA11 GNAQ HLA immunotherapy neoantigen uveal melanoma |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2261278 |
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