A computer tool analyses in detail the genetic alterations in the genome of cancer cells.

Oct 15, 2022 | Current affairs, Featured, Post, Revista Lloseta, Thursday Daily Bulletin, Tradition, Uncategorized

Developed by the CSIC, CiberAMP allows direct correlations to be established between changes in the number of copies of genes in tumour cells and their levels of expression.

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A team of researchers from the Salamanca Cancer Research Centre (CIC-CSIC-US), a joint institute of the Spanish National Research Council (CSIC) and the University of Salamanca, has developed a new computer tool, called CiberAMP, to analyse genetic alterations in the genome of cancer cells in greater detail. The tool makes it possible to establish, for the first time, direct correlations between changes in the number of gene copies that occur in tumour cells and their expression levels, as well as to identify genetic alterations with a direct role in cancer development. The work has been carried out by the laboratory led by CSIC researcher Xosé Bustelo, from the CIC-CSIC-US, the Centro de Investigación Biomédica en Red de Cáncer (CIBERONC-CSIC-US) and the CSIC Cancer Connection. It is published in the journal Biology.

“This new tool, which is easy to use by any user without the need for extensive computer knowledge, provides information on the degree of correlation between the change in the number of gene copies and their expression levels using genomic data available for 33 different types of tumours obtained from the study of more than 11,000 patients,” explains Rubén Caloto, a researcher at CIBERONC-CSIC-US and lead author of this work. Furthermore,” says Caloto, “it allows us to know the genomic context of these genetic alterations, which gives us very valuable information to know whether these altered genes have important functions in the development of these tumours. And it is also very flexible since with it we can study a specific gene in a specific tumour or, alternatively, thousands of genes in any tumour or group of tumours we want.

New tools
The characterisation of the genome of major tumours has led to the discovery of thousands of associated genetic alterations. Many are point changes in our genome that can result in the activation or inactivation of genes that favour or antagonise cancer development, respectively. However, in many other cases, these genetic alterations do not involve point changes, but changes in the number of copies of various-sized pieces of our chromosomes, the structure that houses our DNA within cells. The functional significance of this second type of genetic alteration, which may involve the gain or loss of the genes involved in these chromosomal changes, is difficult to establish.

In principle, it is assumed that a gene that has increased its copy number could help the development of cancer. Alternatively, genes that have been deleted could be associated with suppressive functions in tumour development. However, a gene with no role in cancer development may increase its copy number simply because it is close to a gene that plays a key role in cancer development. Likewise, many genetic alterations are of no real value, since only those that determine changes in the expression of the genes contained in the chromosomal alteration can contribute to changes in cellular behaviour. This is not always the case. For example, there are cases in which the gain in gene copy number does not translate into changes in the expression of these genes. Knowing which are the key elements in this process is essential to subsequently develop new diagnostics and treatments specifically targeting these tumours.

To solve this problem, new informatics tools are needed that, using currently available genetic information from multiple tumours and patients, can provide information on the correlation between gene copy number changes and gene expression levels in cancer cells. These tools are also needed to provide information on the genes contained in these chromosomal alterations in order to identify those that play important roles in the development or malignancy of specific tumours.

Genetic alterations linked to glioblastoma
To demonstrate the usefulness of this new bioinformatics tool, the research group used CyberAMP to analyse the possible functional significance of genetic alterations linked to gene copy number change in a brain tumour called glioblastoma. “The use of CyberAMP allowed us to discover 74 genes that may play a key role in the development of this tumour type. Of these genes, 38 were already known to be involved in this or other tumours, which is logical given the large number of studies that have been carried out on cancer in recent decades. However, the remaining 36 genes identified are new, which means that we will have to focus on their study in the coming years,” says Bustelo.

“The interesting thing, the second author of the article, is that this type of study can be done for any other tumour type for which genomic data are available from a significant number of patients, which makes it suitable for general use by any researcher or oncologist,” says Francisco Lorenzo-Martín, a scientist at the CIC-CSIC-US and second author of the article. To facilitate this general use, the new software tool is freely available to the public. And it can be installed on any computer.

The groups of Víctor Quesada, from the University of Oviedo and the CIBERONC, and Arkait Carracedo, an IkerBasque scientist at the CIC-Biogune in Derio (Bilbao) and also belonging to the CIBERONC, have collaborated in this work. The research is part of the objectives of the CIBERONC’s Tumour Progression Mechanisms Programme and has been made possible thanks to funding from the State Research Agency, the Carlos III Health Institute, the La Caixa Foundation, the Spanish Association for Cancer Research and the Ministry of Education of the Regional Government of Castilla y León. The activities of the Salamanca Cancer Research Centre are also supported by the Escalera de Excelencia of the Junta de Castilla y León and FEDER funds.