Genetic and Molecular Characterization of Nervous System Lesions

Over the past 15 years, knowledge of these tumors has increased exponentially, thanks to the genomic revolution (high-throughput sequencing, methylome analysis), which has improved their classification, defining homogeneous prognostic, predictive and even theranostic groups (BRAF, FGFR, NTRK). This knowledge has only progressed thanks to access to tumor samples, but also to constitutional DNA and liquid biopsies.

The histo-pronostic classification of these tumors is constantly evolving, as evidenced by the new WHO 2021 version, which integrates more and more molecular markers for diagnosis (in which the team participated), and considerably modifies nosological frameworks. This process began with the 2007 classification, which was purely morphological and particularly unsatisfactory, with over 30% inter-observer diagnostic discordance, and the 2016 version has considerably clarified the classification of grade 2 and 3 gliomas, by integrating biomarkers that are now unavoidable, such as 1p19q codeletion and IDH1 and IDH2 mutation: however, it has taken several years for these markers to be routinely performed and managed. The extremely rapid evolution of diagnostic criteria is illustrated by the c-impact now initiative, which has regularly revisited the classification of primary brain tumours, and gliomas in particular, in the light of the most recent publications, and on which the 2021 classification is based: however, certain data are still fragile and criticized because they are based on limited series (for example, the definition of grade 2 gliomas, reclassified as "molecular glioblastomas".

Glioblastoma and other diffuse gliomas are incurable, lethal diseases that are resistant to conventional treatments (radiotherapy, chemotherapy). Compared with other cancers, the number of effective treatments and therefore treatment lines available is limited. The longitudinal study of these diseases is essential to understanding the mechanisms of resistance to treatment and identifying new vulnerabilities. Our team actively contributes to this research, for which tumor samples at initial diagnosis, but also at recurrence and possibly post-mortem are invaluable.

Given its strengths, our team can now make a decisive contribution to improving diagnosis and prediction in the management of primary brain tumors.

First and foremost, the team represents Europe's leading center for the management of glioma patients. Between 10% and 15% of patients with primary brain tumors in France are treated in Neuro-oncology at La Salpêtrière.