Interferon signaling promotes tolerance to chromosomal instability during metastatic evolution in renal cancer
© 2023. The Author(s)..
Molecular routes to metastatic dissemination are critical determinants of aggressive cancers. Through in vivo CRISPR-Cas9 genome editing, we generated somatic mosaic genetically engineered models that faithfully recapitulate metastatic renal tumors. Disruption of 9p21 locus is an evolutionary driver to systemic disease through the rapid acquisition of complex karyotypes in cancer cells. Cross-species analysis revealed that recurrent patterns of copy number variations, including 21q loss and dysregulation of the interferon pathway, are major drivers of metastatic potential. In vitro and in vivo genomic engineering, leveraging loss-of-function studies, along with a model of partial trisomy of chromosome 21q, demonstrated a dosage-dependent effect of the interferon receptor genes cluster as an adaptive mechanism to deleterious chromosomal instability in metastatic progression. This work provides critical knowledge on drivers of renal cell carcinoma progression and defines the primary role of interferon signaling in constraining the propagation of aneuploid clones in cancer evolution.
| Errataetall: |
CommentIn: Trends Cancer. 2023 Nov;9(11):871-873. - PMID 37658022 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:4 |
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| Enthalten in: |
Nature cancer - 4(2023), 7 vom: 12. Juli, Seite 984-1000 |
| Sprache: |
Englisch |
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| Links: |
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Journal Article |
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| Anmerkungen: |
Date Completed 27.07.2023 Date Revised 10.02.2024 published: Print-Electronic figshare: 10.6084/m9.figshare.21637199.v2 CommentIn: Trends Cancer. 2023 Nov;9(11):871-873. - PMID 37658022 Citation Status MEDLINE |
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| doi: |
10.1038/s43018-023-00584-1 |
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| 245 | 1 | 0 | |a Interferon signaling promotes tolerance to chromosomal instability during metastatic evolution in renal cancer |
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| 500 | |a figshare: 10.6084/m9.figshare.21637199.v2 | ||
| 500 | |a CommentIn: Trends Cancer. 2023 Nov;9(11):871-873. - PMID 37658022 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023. The Author(s). | ||
| 520 | |a Molecular routes to metastatic dissemination are critical determinants of aggressive cancers. Through in vivo CRISPR-Cas9 genome editing, we generated somatic mosaic genetically engineered models that faithfully recapitulate metastatic renal tumors. Disruption of 9p21 locus is an evolutionary driver to systemic disease through the rapid acquisition of complex karyotypes in cancer cells. Cross-species analysis revealed that recurrent patterns of copy number variations, including 21q loss and dysregulation of the interferon pathway, are major drivers of metastatic potential. In vitro and in vivo genomic engineering, leveraging loss-of-function studies, along with a model of partial trisomy of chromosome 21q, demonstrated a dosage-dependent effect of the interferon receptor genes cluster as an adaptive mechanism to deleterious chromosomal instability in metastatic progression. This work provides critical knowledge on drivers of renal cell carcinoma progression and defines the primary role of interferon signaling in constraining the propagation of aneuploid clones in cancer evolution | ||
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| 700 | 1 | |a Zhang, Li |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Justin K |e verfasserin |4 aut | |
| 700 | 1 | |a Le, Courtney |e verfasserin |4 aut | |
| 700 | 1 | |a Khan, Hania |e verfasserin |4 aut | |
| 700 | 1 | |a Citron, Francesca |e verfasserin |4 aut | |
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