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Figure 2 Effect of chromosomal instability tolerance
and attenuation on the propagation of cells with complex karyotypes Figure 2 | Effect of chromosomal instability tolerance and attenuation on the propagation of cells with complex karyotypes. a | Cells without chromosomal instability (CIN) with functional stress response pathways will maintain a stable karyotype. Rare stochastic chromosome segregation errors are likely to be outcompeted but could persist. b | CIN occurring in the presence of functional stress response pathways, including activation of p53, will prevent the propagation of cells with complex karyotypes. Only aneuploidies involving specific chromosomes are likely to be tolerated, and cellswill proliferate at a much slower rate. c | CIN tolerance enables rare stochastic errors from an otherwise karyotypically stable population to be efficiently propagated. Additional numerical and structural aberrations can then be acquired and propagated. d | High levels of CIN, despite mutations conferring CIN tolerance, will generate an increasing number of cells with unviable karyotypes and are therefore considered tumour suppressive. e | Alterations leading to a transient or less penetrant CIN phenotype will reduce the frequency of unviable karyotypes. Cells with CIN might also acquire secondary mutations that reduce both the incidence and severity of chromosome segregation errors, thus improving cellular fitness. S-CIN, structurally aberrant CIN; SCNAs, somatic copy-number alterations; W-CIN, whole-chromosome CIN. Sansregret, L. et al. (2017) Determinants and clinical implications of chromosomal instability in cancer Nat. Rev. Clin. Oncol. doi: /nrclinonc
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