What are the biological mechanisms of brain tumours?

In general, cancer is linked to the occurrence of successive mutations in a given cell and in specific genes responsible for the proliferation of the cells that form the tumour. These mutations are present only in the cancer cells and not in the whole organism. They are therefore not hereditary.
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In the case of gliomas, a mutation of a gene in a particular cell, an oligodendrocyte for example, and only in this cell type and not in all the cells of the body, leads to its multiplication.

The team led by Prof Marc SANSON and Dr Emmanuelle HUILLARD is seeking to characterise the mutations in each cell type at the origin of brain tumours. The search for these mutations is carried out in the cancer cells themselves after biopsy or surgery on the tumour.

This research involves sequencing, i.e. reading, the entire DNA of a cell and comparing it with that of a normal cell from the same individual. DNA sequence differences can then be identified, corresponding to mutations that have occurred in the tumour: some of these alter the normal functioning of the cell, in particular cell proliferation.

Thanks to the genotyping/sequencing platform at the Institut du Cerveau – ICM, it is now possible to read the entire DNA of a very small number of cells very reliably and in just a few hours, compared with several weeks previously.

The Institut du Cerveau – ICM has also developed a faster molecular diagnostic technology, called nanopore sequencing. This technique makes it possible to study structural variants, single mutations and the methylation profile, an epigenetic characteristic, over a one-day period, using a single tool and at a lower cost.

The identification of these mutations at the origin of brain tumours enables :

  • Precise diagnosis of the tumour
  • An understanding of the mechanisms behind tumours
  • Identify new therapeutic avenues.

At the Paris Brain Institute

Researchers in the team led by Prof Marc SANSON and Dr Emmanuelle HUILLARD have focused on a number of specific subtypes of glioma: midline gliomas of the brain and spinal cord in adults. They identified a mutation present in 20% of cases in the FGFR1 gene. Specific treatments targeting this gene are now available; chordoid gliomas characterised by a very specific mutation (Rosenberg), gliomas with genetic instability that would make them vulnerable to specific treatments including immunotherapy (Touat, Nature), gliomas characterised by a significant inflammatory response, etc. (Hernandez, Ann Oncol).

The team has also generated important results in two other tumour types: primary brain lymphomas, proposing a molecular classification that is prognostic and predictive of response to treatment (Hernandez, Ann Oncol), and meningiomas…