A research team led by Nuno Barbosa Morais, group leader at Instituto de Medicina Molecular João Lobo Antunes (iMM) in Lisbon, computationally analysed the expression of marker genes that are associated with a "fingerprint" of cancer cells in thousands of tumours and revealed its therapeutic potential in the fight against cancer. The study published in the scientific journal PLoS Computational Biology shows the types of tumours in which these genes are most active and identifies drugs with the potential to selectively eliminate cells that carry that label.
Authors and Affiliations:
Bernardo P. de Almeida — Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
André F. Vieira — i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal, IPATIMUP - Instituto de Patologia e Imunologia Molecular, Universidade do Porto, Porto, Portugal
Joana Paredes — i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal, IPATIMUP - Instituto de Patologia e Imunologia Molecular, Universidade do Porto, Porto, Portugal
Mónica Bettencourt-Dias — Instituto Gulbenkian de Ciência, Oeiras, Portugal
Nuno L. Barbosa-Morais — Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
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.
Journal: PLoS Computational Biology