Inactivation of RB1, CDKN2A and TP53 have distinct effects on genomic stability at side-by-side comparison in karyotypically normal cells

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

Sammanfattning

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.
Originalspråkengelska
Sidor (från-till)93-100
TidskriftGenes, Chromosomes and Cancer
Volym62
Nummer2
Tidigt onlinedatum2022 sep. 20
DOI
StatusPublished - 2023

Ämnesklassifikation (UKÄ)

  • Cancer och onkologi
  • Medicinsk genetik

Fingeravtryck

Utforska forskningsämnen för ”Inactivation of RB1, CDKN2A and TP53 have distinct effects on genomic stability at side-by-side comparison in karyotypically normal cells”. Tillsammans bildar de ett unikt fingeravtryck.

Citera det här