Identification of genetic fingerprint of type I interferon therapy in visceral metastases of melanoma
Abstract Malignant melanoma is a difficult-to-treat skin cancer with increasing incidence worldwide. Although type-I interferon (IFN) is no longer part of guidelines, several melanoma patients are treated with type-I interferon (IFN) at some point of the disease, potentially affecting its genetic pr...
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Nature Portfolio
2024-11-01
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| Online Access: | https://doi.org/10.1038/s41598-024-77285-x |
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| author | Laura Vízkeleti Orsolya Papp Viktória Doma Jeovanis Gil György Markó-Varga Szonja A. Kovács Balázs Győrffy Sarolta Kárpáti József Tímár |
| author_facet | Laura Vízkeleti Orsolya Papp Viktória Doma Jeovanis Gil György Markó-Varga Szonja A. Kovács Balázs Győrffy Sarolta Kárpáti József Tímár |
| author_sort | Laura Vízkeleti |
| collection | DOAJ |
| description | Abstract Malignant melanoma is a difficult-to-treat skin cancer with increasing incidence worldwide. Although type-I interferon (IFN) is no longer part of guidelines, several melanoma patients are treated with type-I interferon (IFN) at some point of the disease, potentially affecting its genetic progression. We run genome-wide copy number variation (CNV) analysis on previously type-I IFN-treated (n = 17) and control (n = 11) visceral metastases of melanoma patients. Results were completed with data from the TCGA and MM500 databases. We identified metastasis- and brain metastasis-specific gene signatures mostly affected by CN gains. Some cases were genetically resistant to IFN showing characteristic gene alterations (e.g. ABCA4 or ZEB2 gain and alterations of DNA repair genes). Analysis of a previously identified type-I IFN resistance gene set indicates that only a proportion of these genes was exclusive for the IFN-treated metastases reflecting a possible selective genomic pressure of endogenous IFNs during progression. Our data suggest that previous type-I IFN treatment and/or endogenous IFN production by immune response affect genomic progression of melanoma which may have clinical relevance, potentially influence immune checkpoint regulation in the tumor microenvironment. |
| format | Article |
| id | doaj-art-c19738d85de242578f64a9a66457ea73 |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-c19738d85de242578f64a9a66457ea732025-08-20T02:13:24ZengNature PortfolioScientific Reports2045-23222024-11-0114111610.1038/s41598-024-77285-xIdentification of genetic fingerprint of type I interferon therapy in visceral metastases of melanomaLaura Vízkeleti0Orsolya Papp1Viktória Doma2Jeovanis Gil3György Markó-Varga4Szonja A. Kovács5Balázs Győrffy6Sarolta Kárpáti7József Tímár8Department of Bioinformatics, Faculty of Medicine, Semmelweis UniversityDepartment of Pathology, Forensic and Insurance Medicine, Faculty of Medicine, Semmelweis UniversityDepartment of Pathology, Forensic and Insurance Medicine, Faculty of Medicine, Semmelweis UniversityClinical Protein Science & Imaging, Biomedical Centre, Department of Biomedical Engineering, Lund UniversityClinical Protein Science & Imaging, Biomedical Centre, Department of Biomedical Engineering, Lund UniversityDepartment of Bioinformatics, Faculty of Medicine, Semmelweis UniversityDepartment of Bioinformatics, Faculty of Medicine, Semmelweis UniversityDepartment of Dermatology, Venerology and Dermato-Oncology, Faculty of Medicine, Semmelweis UniversityDepartment of Pathology, Forensic and Insurance Medicine, Faculty of Medicine, Semmelweis UniversityAbstract Malignant melanoma is a difficult-to-treat skin cancer with increasing incidence worldwide. Although type-I interferon (IFN) is no longer part of guidelines, several melanoma patients are treated with type-I interferon (IFN) at some point of the disease, potentially affecting its genetic progression. We run genome-wide copy number variation (CNV) analysis on previously type-I IFN-treated (n = 17) and control (n = 11) visceral metastases of melanoma patients. Results were completed with data from the TCGA and MM500 databases. We identified metastasis- and brain metastasis-specific gene signatures mostly affected by CN gains. Some cases were genetically resistant to IFN showing characteristic gene alterations (e.g. ABCA4 or ZEB2 gain and alterations of DNA repair genes). Analysis of a previously identified type-I IFN resistance gene set indicates that only a proportion of these genes was exclusive for the IFN-treated metastases reflecting a possible selective genomic pressure of endogenous IFNs during progression. Our data suggest that previous type-I IFN treatment and/or endogenous IFN production by immune response affect genomic progression of melanoma which may have clinical relevance, potentially influence immune checkpoint regulation in the tumor microenvironment.https://doi.org/10.1038/s41598-024-77285-xType-I interferonCNVMalignant melanomaVisceral metastases |
| spellingShingle | Laura Vízkeleti Orsolya Papp Viktória Doma Jeovanis Gil György Markó-Varga Szonja A. Kovács Balázs Győrffy Sarolta Kárpáti József Tímár Identification of genetic fingerprint of type I interferon therapy in visceral metastases of melanoma Scientific Reports Type-I interferon CNV Malignant melanoma Visceral metastases |
| title | Identification of genetic fingerprint of type I interferon therapy in visceral metastases of melanoma |
| title_full | Identification of genetic fingerprint of type I interferon therapy in visceral metastases of melanoma |
| title_fullStr | Identification of genetic fingerprint of type I interferon therapy in visceral metastases of melanoma |
| title_full_unstemmed | Identification of genetic fingerprint of type I interferon therapy in visceral metastases of melanoma |
| title_short | Identification of genetic fingerprint of type I interferon therapy in visceral metastases of melanoma |
| title_sort | identification of genetic fingerprint of type i interferon therapy in visceral metastases of melanoma |
| topic | Type-I interferon CNV Malignant melanoma Visceral metastases |
| url | https://doi.org/10.1038/s41598-024-77285-x |
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