Luciano Di Croce – Centre de Regulació Genòmica (CRG)

1% of all childhood cancers are Ewing tumors. It mainly affects children and adolescents, but is also seen in young adults, with males slightly more affected than females.

Researchers at the Centre for Genomic Regulation (CRG) and the Institut de Recerca Sant Joan de Déu have found that the RING1B gene is critical for the development of Ewing sarcoma, a rare type of cancer that affects bones or the tissue around bones and it account for 1% of all childhood cancers. This newly uncovered epigenetic vulnerability in Ewing sarcoma cancer cells opens the opportunity for new therapeutic strategies.

The new study published in Science Advances reports that RING1B and EWSR1-FLI1 localize at the same regions in the genome, where RING1B is responsible for EWSR1-FLI1 recruitment. EWSR1- FLI1 cannot activate its target genes and transform a cell without RING1B.

Base on this common interested the Centre for Genomic Regulation (CRG) and the Institut de Recerca Sant Joan de Déu want to extend the investigation to brainstem glioma, which mainly affects children, and at the moment there is no treatment, and it has a poor prognosis.

The tumor is made up of very different cells that vary from patient to patient, and even change during the course of the disease itself. This makes it difficult to find an effective treatment.

Until now, research on this tumor has been based on studies at the individualized cell level. Instead, the project cooridnated by Dr Luciano Di Croce in collaboration with Dr Mora (HSJD) and Dr. Marti- Renom (ICREA), and sponsored by la Caixa proposes multicellular reconstruction of the tumor in 3D, using personalized models of the patient in mice (PDX-patient derived xenograft). These models will allow testing individualized treatments for this type of cancer.

Sanchez-Molina S; Figuerola-Bou E, Blanco E, Sanchez-Jimenez M, Taboas P, Gomez S, Ballare C, Garcia-Dominguez DJ, Prada E, Hontecillas-Prieto L, Carcaboso AM, Tirado OM, Hernandez- Munoz I, de Alava E, Lavarino C, Di Croce L* & Mora J* 2020, ‘RING1B recruits EWSR1-FLI1 and cooperates in the remodeling of chromatin necessary for Ewing sarcoma tumorigenesis’, Science Advances, 6, 43, eaba3058.