Patterns of structural variants within TP53 introns and relocation of the TP53 promoter: a commentary†
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2024
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| _version_ | 1867020714484170753 |
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| author | Hannah C Beird Dimitri Lin Alexander J Lazar P Andrew Futreal |
| author_facet | Hannah C Beird Dimitri Lin Alexander J Lazar P Andrew Futreal Hannah C Beird Dimitri Lin Alexander J Lazar P Andrew Futreal |
| collection | Wiley Open Access |
| contents | Patterns of structural variants within TP53 introns and relocation of the TP53 promoter: a commentary† Hannah C Beird Dimitri Lin Alexander J Lazar P Andrew Futreal The Journal of Pathology AbstractGene disruption from double‐strand DNA breaks within introns is a mechanism of inactivating the tumor suppressor TP53. This occurs more frequently in osteosarcoma and biliary adenocarcinoma compared with other cancer types. The patterns of intron breakpoints within TP53 do not correlate with prevalence, intron length, or overall genome‐wide levels of rearrangements. Therefore, these breakpoints appear to be selected for reasons other than to disrupt TP53. A recent article published by Saba et al in The Journal of Pathology illustrates a benefit to having breakpoints within intron 1 using high‐quality matched genomic and transcriptomic osteosarcoma sequencing data as well as in vitro validation. The authors describe how the rearrangement results in relocation of the TP53 promoter region to regions upstream of genes that encode members of cartilage, growth plate development, osteoclast formation, and other TP53‐related pathways. The upregulation of these genes by the TP53 promoter are gain‐of‐function events that are likely to promote tumor development and growth. Therefore, this article presents a potential new paradigm in which a single mutation would result in both the loss of a tumor suppressor and the gain of an oncogenic program. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. 10.1002/path.6270 http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| doi_str_mv | 10.1002/path.6270 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_path_6270 |
| institution | Wiley Open Access |
| license_str_mv | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| publishDate | 2024 |
| publisher | Wiley |
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| spellingShingle | Patterns of structural variants within TP53 introns and relocation of the TP53 promoter: a commentary† Hannah C Beird Dimitri Lin Alexander J Lazar P Andrew Futreal The Journal of Pathology Patterns of structural variants within TP53 introns and relocation of the TP53 promoter: a commentary† Hannah C Beird Dimitri Lin Alexander J Lazar P Andrew Futreal The Journal of Pathology AbstractGene disruption from double‐strand DNA breaks within introns is a mechanism of inactivating the tumor suppressor TP53. This occurs more frequently in osteosarcoma and biliary adenocarcinoma compared with other cancer types. The patterns of intron breakpoints within TP53 do not correlate with prevalence, intron length, or overall genome‐wide levels of rearrangements. Therefore, these breakpoints appear to be selected for reasons other than to disrupt TP53. A recent article published by Saba et al in The Journal of Pathology illustrates a benefit to having breakpoints within intron 1 using high‐quality matched genomic and transcriptomic osteosarcoma sequencing data as well as in vitro validation. The authors describe how the rearrangement results in relocation of the TP53 promoter region to regions upstream of genes that encode members of cartilage, growth plate development, osteoclast formation, and other TP53‐related pathways. The upregulation of these genes by the TP53 promoter are gain‐of‐function events that are likely to promote tumor development and growth. Therefore, this article presents a potential new paradigm in which a single mutation would result in both the loss of a tumor suppressor and the gain of an oncogenic program. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. 10.1002/path.6270 http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| title | Patterns of structural variants within TP53 introns and relocation of the TP53 promoter: a commentary† |
| topic | The Journal of Pathology |
| url | https://pathsocjournals.onlinelibrary.wiley.com/doi/10.1002/path.6270 |