Gamma-Retrovirus Integration Marks Cell Type-Specific Cancer Genes: A Novel Profiling Tool in Cancer Genomics.
Retroviruses have been foundational in cancer research since early studies identified proto-oncogenes as targets for insertional mutagenesis. Integration of murine gamma-retroviruses into the host genome favours promoters and enhancers and entails interaction of viral integrase with host BET/bromodo...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0154070&type=printable |
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| author | Kathryn L Gilroy Anne Terry Asif Naseer Jeroen de Ridder Amin Allahyar Weiwei Wang Eric Carpenter Andrew Mason Gane K-S Wong Ewan R Cameron Anna Kilbey James C Neil |
| author_facet | Kathryn L Gilroy Anne Terry Asif Naseer Jeroen de Ridder Amin Allahyar Weiwei Wang Eric Carpenter Andrew Mason Gane K-S Wong Ewan R Cameron Anna Kilbey James C Neil |
| author_sort | Kathryn L Gilroy |
| collection | DOAJ |
| description | Retroviruses have been foundational in cancer research since early studies identified proto-oncogenes as targets for insertional mutagenesis. Integration of murine gamma-retroviruses into the host genome favours promoters and enhancers and entails interaction of viral integrase with host BET/bromodomain factors. We report that this integration pattern is conserved in feline leukaemia virus (FeLV), a gamma-retrovirus that infects many human cell types. Analysis of FeLV insertion sites in the MCF-7 mammary carcinoma cell line revealed strong bias towards active chromatin marks with no evidence of significant post-integration growth selection. The most prominent FeLV integration targets had little overlap with the most abundantly expressed transcripts, but were strongly enriched for annotated cancer genes. A meta-analysis based on several gamma-retrovirus integration profiling (GRIP) studies in human cells (CD34+, K562, HepG2) revealed a similar cancer gene bias but also remarkable cell-type specificity, with prominent exceptions including a universal integration hotspot at the long non-coding RNA MALAT1. Comparison of GRIP targets with databases of super-enhancers from the same cell lines showed that these have only limited overlap and that GRIP provides unique insights into the upstream drivers of cell growth. These observations elucidate the oncogenic potency of the gamma-retroviruses and support the wider application of GRIP to identify the genes and growth regulatory circuits that drive distinct cancer types. |
| format | Article |
| id | doaj-art-fffeecc2b77e4c0dbb2b30242dabfe8a |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-fffeecc2b77e4c0dbb2b30242dabfe8a2025-08-20T02:03:13ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01114e015407010.1371/journal.pone.0154070Gamma-Retrovirus Integration Marks Cell Type-Specific Cancer Genes: A Novel Profiling Tool in Cancer Genomics.Kathryn L GilroyAnne TerryAsif NaseerJeroen de RidderAmin AllahyarWeiwei WangEric CarpenterAndrew MasonGane K-S WongEwan R CameronAnna KilbeyJames C NeilRetroviruses have been foundational in cancer research since early studies identified proto-oncogenes as targets for insertional mutagenesis. Integration of murine gamma-retroviruses into the host genome favours promoters and enhancers and entails interaction of viral integrase with host BET/bromodomain factors. We report that this integration pattern is conserved in feline leukaemia virus (FeLV), a gamma-retrovirus that infects many human cell types. Analysis of FeLV insertion sites in the MCF-7 mammary carcinoma cell line revealed strong bias towards active chromatin marks with no evidence of significant post-integration growth selection. The most prominent FeLV integration targets had little overlap with the most abundantly expressed transcripts, but were strongly enriched for annotated cancer genes. A meta-analysis based on several gamma-retrovirus integration profiling (GRIP) studies in human cells (CD34+, K562, HepG2) revealed a similar cancer gene bias but also remarkable cell-type specificity, with prominent exceptions including a universal integration hotspot at the long non-coding RNA MALAT1. Comparison of GRIP targets with databases of super-enhancers from the same cell lines showed that these have only limited overlap and that GRIP provides unique insights into the upstream drivers of cell growth. These observations elucidate the oncogenic potency of the gamma-retroviruses and support the wider application of GRIP to identify the genes and growth regulatory circuits that drive distinct cancer types.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0154070&type=printable |
| spellingShingle | Kathryn L Gilroy Anne Terry Asif Naseer Jeroen de Ridder Amin Allahyar Weiwei Wang Eric Carpenter Andrew Mason Gane K-S Wong Ewan R Cameron Anna Kilbey James C Neil Gamma-Retrovirus Integration Marks Cell Type-Specific Cancer Genes: A Novel Profiling Tool in Cancer Genomics. PLoS ONE |
| title | Gamma-Retrovirus Integration Marks Cell Type-Specific Cancer Genes: A Novel Profiling Tool in Cancer Genomics. |
| title_full | Gamma-Retrovirus Integration Marks Cell Type-Specific Cancer Genes: A Novel Profiling Tool in Cancer Genomics. |
| title_fullStr | Gamma-Retrovirus Integration Marks Cell Type-Specific Cancer Genes: A Novel Profiling Tool in Cancer Genomics. |
| title_full_unstemmed | Gamma-Retrovirus Integration Marks Cell Type-Specific Cancer Genes: A Novel Profiling Tool in Cancer Genomics. |
| title_short | Gamma-Retrovirus Integration Marks Cell Type-Specific Cancer Genes: A Novel Profiling Tool in Cancer Genomics. |
| title_sort | gamma retrovirus integration marks cell type specific cancer genes a novel profiling tool in cancer genomics |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0154070&type=printable |
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