"Length matters: Causes and consequences of centriole length deregulation in cancer"

Financiador

Organização

Publicações

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

Publication . Almeida, Bernardo P. De; Vieira, André F.; Paredes, Joana; Bettencourt-Dias, Mónica; Barbosa-Morais, Nuno

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.

2019Artigo científico

Acesso aberto

Ver mais

Entidade financiadora

Fundação para a Ciência e a Tecnologia

Programa de financiamento

3599-PPCDT

Número da atribuição

PTDC/BIM-ONC/6858/2014