A new class of RNAs and the centrosomal hypothesis of cell aging

Chichinadze, Konstantin; Tkemaladze, Jaba; Lazarashvili, Ann

doi:10.1134/s2079057012040054

Cited by 1 publication

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“…The latter is supported by recent work showing that human chromosome mis-segregation is not random and can be biased by inherent properties of individual chromosomes [ 62 ], and also by our observation that normal samples whose matched tumours lost 5q or 16p have higher CA20 predictive of those deletions ( S6 Fig ). Moreover, we characterised the DNA mutation spectrum associated with CA20 and found it to be enriched in C>T mutations, a signature characteristic of ageing, with which centrosome aberrations have also been associated [ 63 – 67 ]. Genes whose mutations are associated with CA20 are enriched in cancer driver genes, and particularly in Wnt/β-catenin signalling.…”

Section: Discussionmentioning

confidence: 99%

Pan-cancer association of a centrosome amplification gene expression signature with genomic alterations and clinical outcome

et al. 2019

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Centrosome amplification (CA) is a common feature of human tumours and a promising target for cancer therapy. However, CA’s pan-cancer prevalence, molecular role in tumourigenesis and therapeutic value in the clinical setting are still largely unexplored. Here, we used a transcriptomic signature (CA20) to characterise the landscape of CA-associated gene expression in 9,721 tumours from The Cancer Genome Atlas (TCGA). CA20 is upregulated in cancer and associated with distinct clinical and molecular features of breast cancer, consistently with our experimental CA quantification in patient samples. Moreover, we show that CA20 upregulation is positively associated with genomic instability, alteration of specific chromosomal arms and C>T mutations, and we propose novel molecular players associated with CA in cancer. Finally, high CA20 is associated with poor prognosis and, by integrating drug sensitivity with drug perturbation profiles in cell lines, we identify candidate compounds for selectively targeting cancer cells exhibiting transcriptomic evidence for CA.

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Section: Discussionmentioning

confidence: 99%