The Computational Genomics research group at Pompeu Fabra University has discovered new alterations linked to cancer and has revealed the importance of transcriptome in the development of tumours. For the first time, scientists have studied the variability of cell transcriptome in several tumours at the same time, that is to say, not focusing on DNA but on the products extracted from it. The results of the study have been published in the journal Genome Research.

The genetic information of cells is encoded in the DNA strand. This information is read by the cellular machinery, which will generate the so-called RNA to then translate it to proteins. Sometimes, the same gene can give rise to different RNA molecules, which produce different proteins with potentially very different functions. This is due to a process known as “alternative splicing”, which influences the synthesis of most of the proteins of eukaryotic cells and their regulation depends on the RNA-binding proteins (RBPs).

Despite the importance of alternative splicing in cell functioning being widely known by the scientific community, the role it plays in cancer has just begun to emerge. This has been possible thanks to new sequencing techniques and the availability of RNA sequencing data of multiple tumours through projects such as The Cancer Genome Atlas (TCGA). Although cancer originates from mutations in DNA, they have an impact on the set of RNA molecules of the cell, known as transcriptome, which can induce and maintain mechanisms linked to the development of cancer. The research team led by Eduardo Eyras, head of the Computational Genomics laboratory, has unveiled some alterations in RBPs which bring about changes in alternative splicing linked with the development of cancer.

Thanks to the bioinformatics tools designed by the research group, in record time and using limited computational resources the scientists have been able to carry out a comprehensive analysis of the RNA of over 4,000 tumour samples from eleven different types of cancer taken from the TCGA project. This analysis shows that the proteins bound to the RNA are very often altered in human tumours and that these alterations determine the cell transcriptor and induce cell transformation linked to the development of cancer. Until now, these alterations remained invisible to the methods used in major cancer genome analysis projects.

With the collaboration of doctors Juan Valcárcel and Belén Miñana of the Centre for Genomic Regulation (CRG), and doctors Miguel Ángel Pijuana and Francesca Mateo of the Catalan Institute of Oncology (ICO), the authors have shown that introducing the identified alterations of the transcriptome in non-tumour cells, the latter acquire tumour properties. In addition to expanding our knowledge on the role of RBPs in tumours, the results highlight the importance of alternative splicing as a complementary device in the development of cancer, becoming a new factor to be taken into account in the study of this disease. This research opens up new pathways to understanding the biology of cancer and the search for new therapeutic strategies. As the authors say, “the alterations of alternative splicing are particularly important in the context of those tumours that do not host known mutations and for which no therapy is known, and, therefore, they may open new opportunities to understand tumour biology and search for new therapies.”

This study has been made possible thanks to funding from the Sandra Ibarra Foundation of the Consolider RNAREG project, as well as projects of the State Plan and FEDER funds.

Figure: Splicing regulatory network in genes of the cell cycle in breast cancer. Among other results, the authors have described the network of proteins that interact with the RNA (RBPs) and that increase (red) or decrease (blue) their expression in breast cancer. Some of these genes had been associated with cancer previously (rhombus). In the case of NUMA1, for example, its role in cancer remains unknown. In this study, the authors demonstrate that the alternative splicing of NUMA1 induces tumour properties in normal breast cells.

Reference work: Endre Sebestyén, Babita Singh, Belén Miñana, et al. Large-scale analysis of genome and transcriptome alterations in multiple tumors unveils novel cancer-relevant splicing networks. Genome Research published online April 13, 2016. DOI:10.1101/gr.199935.115

Subscribe to Directory
Write an Article

Recent News

El diagnóstico genético neonatal mejor...

Un estudio con datos de los últimos 35 años, ind...

Más de 1.500 cambios epigenéticos en e...

Un equipo de investigadores de la Universidad Juli...

Tuneable reverse photochromes in the sol...

A new technique allows the design of solid materia...

Highlight

Eosinófilos. ¿Qué significa tener val...

by Labo'Life

​En nuestro post hablamos sobre este interesante tipo de célula del...

Un estudio de INCLIVA muestra el efecto ...

by INCLIVA

Han desarrollado un estudio para evaluar la correlación entre el teji...

Photos Stream