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Inactivation of RB1...
Inactivation of RB1, CDKN2A and TP53 have distinct effects on genomic stability at side-by-side comparison in karyotypically normal cells
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- Andersson, Natalie (författare)
- Lund University,Lunds universitet,Cancercellers evolution,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Pathways of cancer cell evolution,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Saba, Karim (författare)
- Lund University,Lunds universitet,Komplexa kromosomförändringar i cancer,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Genetic chaos in aggressive cancer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Magnusson, Linda (författare)
- Lund University,Lunds universitet,Komplexa kromosomförändringar i cancer,Forskargrupper vid Lunds universitet,Genetiska avvikelser i mjukdelstumörer,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Genetic chaos in aggressive cancer,Lund University Research Groups,The genetics of soft tissue tumors,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Nilsson, Jenny (författare)
- Lund University,Lunds universitet,Komplexa kromosomförändringar i cancer,Forskargrupper vid Lunds universitet,Genetiska avvikelser i mjukdelstumörer,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Genetic chaos in aggressive cancer,Lund University Research Groups,The genetics of soft tissue tumors,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Karlsson, Jenny (författare)
- Lund University,Lunds universitet,Cancercellers evolution,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Pathways of cancer cell evolution,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Hansén Nord, Karolin (författare)
- Lund University,Lunds universitet,Komplexa kromosomförändringar i cancer,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Genetic chaos in aggressive cancer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Gisselsson Nord, David (författare)
- Lund University,Lunds universitet,Cancercellers evolution,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Pathways of cancer cell evolution,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Skåne University Hospital
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(creator_code:org_t)
- 2022-09-30
- 2023
- Engelska.
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 62:2, s. 93-100
- Relaterad länk:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Chromosomal instability is a common feature in malignant tumors. Previous studies have indicated that inactivation of the classical tumor suppressor genes RB1, CDKN2A and TP53 may contribute to chromosomal aberrations in cancer by disrupting different aspects of the cell cycle and DNA damage checkpoint machinery. We performed a side-by-side comparison of how inactivation of each of these genes affected chromosomal stability in vitro. Using CRISPR-Cas9 technology, RB1, CDKN2A and TP53 were independently knocked out in karyotypically normal immortalized cells, after which these cells were followed over time. Bulk RNA sequencing revealed a distinct phenotype with upregulation of pathways related to cell cycle control and proliferation in all three knockouts. Surprisingly, the RB1 and CDKN2A knocked out cell lines did not harbor more copy number aberrations than wild-type cells, despite culturing for months. The TP53-knocked out cells, in contrast, showed a massive amount of copy number alterations and saltatory evolution through whole genome duplication. This side-by-side comparison indicated that the effects on chromosomal stability from inactivation of RB1 and CDKN2A are negligible compared to inactivation of TP53, under the same conditions in a non-stressful environment, even though partly overlapping regulatory pathways are affected.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
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