EDC4 gene involved in familial breast cancer

Breast cancer is one of the most prevalent cancers. It is calculated that some 5-10 percent of these types of cancers are hereditary, often appearing in several members of a family at relatively young ages. The most important genes involved are BRCA1 and BRCA2, discovered in the mid-1990s. BRCA1 is a tumour suppressor gene involved in DNA repair through homologous recombination and in preserving the integrity of the genome. Breast and ovarian tumours lacking one of these two genes are more sensitive to chemotherapy via PARP inhibitors, which are revolutionising drug treatments in this type of cancer. The discovery of new genes involved in these repair mechanisms is very important in order to understand the development of these tumours and delve more deeply into their therapeutic vulnerabilities.

Researchers have demonstrated that the EDC4 gene encodes a protein which interacts with BRCA1 and plays an essential role in DNA repair through the homologous recombination mechanism. By using massive sequencing techniques with more than 1000 breast cancer patients and healthy controls, the researchers observed that the frequency of of EDC4 mutation carriers in patients with familial cancer is six times higher than in healthy individuals. The researchers analysed in detail the effect of these mutations by using advanced engineering and genetic editing techniques and were able to demonstrate that the mutations are pathogenic, impairing the repair capacities of the EDC4 gene. Finally, the authors also demonstrated that cells with mutated EDC4 are highly sensitive to PARP inhibitors, and this presents an opportunity to explore possible therapeutic options for patients with these gene mutations.

Hospital de Sant Pau is a pioneering centre in Spain in the study of BRCA1 and BRCA2 genes in patients with hereditary breast and ovarian cancer. It was also the first hospital in Spain to include genetic analyses of these genes with the aim of offering better assistance to patients and their families. Dr Teresa Ramón y Cajal coordinates the Genetic Counselling Unit of the Medical Oncology Service, directed by Dr Agustí Barnadas. Dr Adriana Lasa coordinates the Oncogenetic Unit of the hospital's Genetic Service, directed by Dr Jordi Surrallés.

More information:
Gonzalo Hernández et al, Decapping protein EDC4 regulates DNA repair and phenocopies BRCA1, Nature Communications (2018). DOI: 10.1038/s41467-018-03433-3

Provided by Autonomous University of Barcelona