Actualité - Pediatric cancers

Childhood cancer: improving the characterization of medulloblastoma

Olivier Ayrault and his team are studying medulloblastoma, a tumor that develops in the cerebellum of young children. Using the latest technological progress, they are improving molecular knowledge about this pediatric tumor.

"Medulloblastoma is the most common malignant brain tumor in children. It develops in the cerebellum," explains Olivier Ayrault, head of the Signaling, development and brain tumors team (CNRS, Inserm, Paris-Saclay university, PSL) at Institut Curie. Now a CNRS director of research, his laboratory is supported by the association "Courir pour la vie, courir pour Curie" and its President Dominique Ancelin to ensure success in the fight against this childhood tumor, which has been at the core of his research since his post-doctoral fellowship at St Jude Children's Research hospital in Memphis, TN.

Indeed despite the progress of treatments, the recovery rate for medulloblastoma remains below 75% and for some sub-types, the rate is even lower. Furthermore, recovery often comes with significant after-effects, particularly in the neuro-cognitive functions.

"We've known for many years that medulloblastoma is a very diverse group of tumors," Olivier explains.  "Four sub-groups have been identified according to the prognosis and the genes expressed. Today, however, the patient care does not systematically include this classification and targeted treatments are almost non-existent". The development of new treatments is a major challenge that cannot be met without a better understanding of the mechanisms involved in the formation of this tumor.

More information for better characterization

Technological developments today provide us access to a wide variety of biological data on tumors. However, to conduct a study on this scale, Olivier Ayrault had to bring in several international teams in Dusseldorf and Toronto, as well as the pediatric neurosurgery department at Necker hospital with Prof. Stéphanie Puget in Paris. The result is that they add a new dimension to the characterization of medulloblastoma, which is proteome.

"Proteome is all the proteins and their chemical variations expressed in a cell," says Antoine Forget, the principal author of this study. The gene is the "chief" that serves to produce proteins in a cell, a single gene may produce several different proteins and each one may then undergo temporary modifications that alter their fate. The proteome is a little-known world, extremely dynamic and even more complex than the genome and the transcriptome. "Proteins are the kingpin of the cells, and give the cell its specific identity," according to Damarys Loew, manager of the proteomics platform at Institut Curie, who contributed to this study. "Integration of the proteome therefore adds a new dimension to the biological studies."

Olivier Ayrault's team has thus incorporated genomics, transcriptomics and proteomics into the study of medulloblastoma. "Then, thanks to a close collaboration with Emmanuel Barillot's bioinformatics team we have been able to make these data speak," observes Olivier Ayrault. "In the end we found signaling pathways activated in the patient only in the proteome. These pathways had remained invisible with only the study of the genome and the transcriptome."

Among the pathways discovered, one of them is specific to a sub-type of medulloblastoma for which no clear signature existed before now, and paves the way for a potential new therapeutic pathway.   


Aberrant ERBB4-SRC Signaling as a Hallmark of Group 4 Medulloblastoma Revealed by Integrative Phosphoproteomic Profiling

Antoine Forget et al.

Cancer Cell vol. 34 issue3 10 September 2018, Pages 379-395.e7