A study led from CiMUS reveals a new mechanism of genomic reorganization in cancer

An international team coordinated from the Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), part of the CIGUS Network — an initiative promoted by the Xunta de Galicia that brings together research centres within the Galician research system that have demonstrated scientific excellence — has identified a mechanism by which mobile fragments of human DNA can trigger large-scale chromosomal rearrangements in tumours.

The study, led by distinguished Oportunius researcher Jose Tubío, has been published in the international journal Science. Its findings were presented on 27 February at CiMUS in an event attended by the Conselleiro de Educación, Ciencia, Universidades y Formación Profesional, Román Rodríguez.

The research shows that LINE-1 (L1) mobile elements, sequences that make up approximately 17% of the human genome, can act as early drivers of chromosomal instability in certain types of cancer. Although most of these elements are inactive, some copies retain the ability to move and insert themselves into new regions of the genome, generating structural alterations.

Using advanced genomic sequencing technologies, the team analysed ten human tumours with high L1 activity and identified more than 6,400 insertion events, of which 152 gave rise to structural variants such as deletions, duplications, inversions and chromosomal translocations. Roughly one in every 40–60 L1 insertions results in this type of structural alteration.

One of the most significant findings is the identification of a mechanism by which simultaneous L1 insertions in different chromosomes can generate reciprocal translocations, a type of structural rearrangement relevant to tumour development that has so far been poorly characterised. The study shows that around 65% of these events occur in the early stages of tumour evolution, reinforcing the role of L1 elements as an early source of genomic instability. These findings open up new avenues for research with potential therapeutic applications.

The study involved national and international institutions, including the Centre for Genomic Regulation (CRG), Université Côte d’Azur, The Francis Crick Institute and the MD Anderson Cancer Center. The research was funded by the Spanish Association Against Cancer, the “la Caixa” Foundation, the Ministry of Science, Innovation and Universities, the Xunta de Galicia and European Regional Development Fund (ERDF) resources.