A Transcriptome-Wide Isoform Landscape of Melanocytic Nevi and Primary Melanomas Identifies Gene Isoforms Associated with Malignancy
Genetic splice variants have become of central interest in recent years, as they play an important role in different cancers. Little is known about splice variants in melanoma. Here, we analyzed a genome-wide transcriptomic dataset of benign melanocytic nevi and primary melanomas (<i>n</i&g...
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MDPI AG
2021-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/13/7165 |
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| author | Siras Hakobyan Henry Loeffler-Wirth Arsen Arakelyan Hans Binder Manfred Kunz |
| author_facet | Siras Hakobyan Henry Loeffler-Wirth Arsen Arakelyan Hans Binder Manfred Kunz |
| author_sort | Siras Hakobyan |
| collection | DOAJ |
| description | Genetic splice variants have become of central interest in recent years, as they play an important role in different cancers. Little is known about splice variants in melanoma. Here, we analyzed a genome-wide transcriptomic dataset of benign melanocytic nevi and primary melanomas (<i>n</i> = 80) for the expression of specific splice variants. Using kallisto, a map for differentially expressed splice variants in melanoma vs. benign melanocytic nevi was generated. Among the top genes with differentially expressed splice variants were Ras-related in brain 6B (<i>RAB6B</i>), a member of the RAS family of GTPases, Macrophage Scavenger Receptor 1 (<i>MSR1</i>), Collagen Type XI Alpha 2 Chain (<i>COLL11A2</i>), and LY6/PLAUR Domain Containing 1 (<i>LYPD1</i>). The Gene Ontology terms of differentially expressed splice variants showed no enrichment for functional gene sets of melanoma vs. nevus lesions, but between type 1 (pigmentation type) and type 2 (immune response type) melanocytic lesions. A number of genes such as Checkpoint Kinase 1 (<i>CHEK1</i>) showed an association of mutational patterns and occurrence of splice variants in melanoma. Moreover, mutations in genes of the splicing machinery were common in both benign nevi and melanomas, suggesting a common mechanism starting early in melanoma development. Mutations in some of these genes of the splicing machinery, such as Serine and Arginine Rich Splicing Factor A3 and B3 (<i>SF3A3</i>, <i>SF3B3</i>), were significantly enriched in melanomas as compared to benign nevi. Taken together, a map of splice variants in melanoma is presented that shows a multitude of differentially expressed splice genes between benign nevi and primary melanomas. The underlying mechanisms may involve mutations in genes of the splicing machinery. |
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| language | English |
| last_indexed | 2024-03-10T09:51:36Z |
| publishDate | 2021-07-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-33422fa946974cca8b69f9d8dd14a56e2023-11-22T02:41:40ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-07-012213716510.3390/ijms22137165A Transcriptome-Wide Isoform Landscape of Melanocytic Nevi and Primary Melanomas Identifies Gene Isoforms Associated with MalignancySiras Hakobyan0Henry Loeffler-Wirth1Arsen Arakelyan2Hans Binder3Manfred Kunz4Institute of Molecular Biology NAS RA, Yerevan 0014, ArmeniaInterdisciplinary Centre for Bioinformatics, University of Leipzig, Härtelstr. 16–18, 04107 Leipzig, GermanyInstitute of Molecular Biology NAS RA, Yerevan 0014, ArmeniaInterdisciplinary Centre for Bioinformatics, University of Leipzig, Härtelstr. 16–18, 04107 Leipzig, GermanyDepartment of Dermatology, Venereology and Allergology, University of Leipzig Medical Center, Philipp-Rosenthal-Str. 23, 04103 Leipzig, GermanyGenetic splice variants have become of central interest in recent years, as they play an important role in different cancers. Little is known about splice variants in melanoma. Here, we analyzed a genome-wide transcriptomic dataset of benign melanocytic nevi and primary melanomas (<i>n</i> = 80) for the expression of specific splice variants. Using kallisto, a map for differentially expressed splice variants in melanoma vs. benign melanocytic nevi was generated. Among the top genes with differentially expressed splice variants were Ras-related in brain 6B (<i>RAB6B</i>), a member of the RAS family of GTPases, Macrophage Scavenger Receptor 1 (<i>MSR1</i>), Collagen Type XI Alpha 2 Chain (<i>COLL11A2</i>), and LY6/PLAUR Domain Containing 1 (<i>LYPD1</i>). The Gene Ontology terms of differentially expressed splice variants showed no enrichment for functional gene sets of melanoma vs. nevus lesions, but between type 1 (pigmentation type) and type 2 (immune response type) melanocytic lesions. A number of genes such as Checkpoint Kinase 1 (<i>CHEK1</i>) showed an association of mutational patterns and occurrence of splice variants in melanoma. Moreover, mutations in genes of the splicing machinery were common in both benign nevi and melanomas, suggesting a common mechanism starting early in melanoma development. Mutations in some of these genes of the splicing machinery, such as Serine and Arginine Rich Splicing Factor A3 and B3 (<i>SF3A3</i>, <i>SF3B3</i>), were significantly enriched in melanomas as compared to benign nevi. Taken together, a map of splice variants in melanoma is presented that shows a multitude of differentially expressed splice genes between benign nevi and primary melanomas. The underlying mechanisms may involve mutations in genes of the splicing machinery.https://www.mdpi.com/1422-0067/22/13/7165melanomasplicingtranscriptometumor progression |
| spellingShingle | Siras Hakobyan Henry Loeffler-Wirth Arsen Arakelyan Hans Binder Manfred Kunz A Transcriptome-Wide Isoform Landscape of Melanocytic Nevi and Primary Melanomas Identifies Gene Isoforms Associated with Malignancy International Journal of Molecular Sciences melanoma splicing transcriptome tumor progression |
| title | A Transcriptome-Wide Isoform Landscape of Melanocytic Nevi and Primary Melanomas Identifies Gene Isoforms Associated with Malignancy |
| title_full | A Transcriptome-Wide Isoform Landscape of Melanocytic Nevi and Primary Melanomas Identifies Gene Isoforms Associated with Malignancy |
| title_fullStr | A Transcriptome-Wide Isoform Landscape of Melanocytic Nevi and Primary Melanomas Identifies Gene Isoforms Associated with Malignancy |
| title_full_unstemmed | A Transcriptome-Wide Isoform Landscape of Melanocytic Nevi and Primary Melanomas Identifies Gene Isoforms Associated with Malignancy |
| title_short | A Transcriptome-Wide Isoform Landscape of Melanocytic Nevi and Primary Melanomas Identifies Gene Isoforms Associated with Malignancy |
| title_sort | transcriptome wide isoform landscape of melanocytic nevi and primary melanomas identifies gene isoforms associated with malignancy |
| topic | melanoma splicing transcriptome tumor progression |
| url | https://www.mdpi.com/1422-0067/22/13/7165 |
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