OncodriveROLE predicts activating and loss of function cancer driver genes

ONCODRIVESWe are pleased to announce that the Oncodrive methods family has a new member: OncodriveROLE, an approach to classify cancer drivers into loss of function and activating roles. OncodriveROLE joins and complements the previously developed methods that identify cancer driver genes from the list of somatic mutations in cohort of tumors (OncodriveCLUST and OncodriveFM).

Cancer driver genes come in two main flavors: those that contain driver alterations which cause the loss of function (LoF) of the gene product (for instance, in tumor suppressor genes like TP53 or CDKN2A), and those with driver alterations that increase or change the activity or function of the protein product, such as oncogenes like PIK3CA or BRAF.

Distinguishing between these two classes of driver genes is very important to understand tumorigenesis in patients and has profound implications for therapeutic decision making and for the development of targeted drugs.

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Exploring the effect of cancer genomic alteration on expression with Gitools

Cancer cells often exhibit a change in number of copies of certain genomic regions when compared to normal cells (Copy Number Alterations: CNAs). Some of these CNAs may have a direct influence on the expression of genes in the affected region. The change in the number of copies of a gene may be both positive, when additional copies are gained (and the genes thus amplified) or negative, when one or more alleles of the gene are lost. The influence of CNAs on the expression of these amplified or lost genes depends on whether it occurs hetero- or homozygously and also on other regulatory factors which may override the effect of the alteration. Therefore, an essential step to verify the importance of the amplification or deletion of a given gene in the tumorigenic process is to verify if its expression tends to respond to its genomic alterations.
Effect of genomic alterations on expression

The effect of genomic alterations can be observed in the expression values. Note for example that samples with loss of CDKN2A shown lower expression values than samples without this alteration. This effect is also evident for the alteration of the other genes.

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