Skip to main content

Or 34,00 After 66% tax deduction

I make a monthly donation I make an IFI donation
Research, science & health

A major role for PIK3CA gene mutations in sporadic cavernoma

Published on: 10/09/2021 Reading time: 1 min
Les cavernomes

Teams from the Paris Brain Institute and Pitié-Salpêtrière Hospital AP-HP, coordinated by Dr Matthieu Peyre and Prof Michel Kalamarides, have studied the presence of mutations in the PIK3CA gene in cavernomas. This work is published in the New England Journal of Medicine.

Cavernomas are low-flow cerebral vascular malformations consisting of abnormally enlarged capillary cavities without intervening brain parenchyma; the condition affects 1 in 200 to 250 people. Although mainly characterised by subclinical bleeding, cavernomas can lead to epileptic seizures and haemorrhagic strokes with significant neurological complications, particularly when they are located in the brainstem.

Cavernomas can occur in isolation or as part of a familial genetic disease. Mutations occurring in a familial context concern in 80% of cases the CCM genes. The genetics of sporadic cavernomas, which account for up to 90% of cases, is poorly understood.

In order to study meningeal tumorigenesis and meningiomas (the most frequent tumour of the central nervous system, of which they are experts), Dr Peyre and Prof Kalamarides have generated two new genetically modified mouse models of meningiomas by activating mutation of the PIK3CA and AKT1 genes in the PI3K-AKT-mTOR pathway.

The unexpected observation of typical cavernomas identical to human lesions prompted them to investigate the possible involvement of PIK3CA and AKT1 mutations in sporadic human cavernomas. They identified 39% PIK3CA mutations in a series of 88 sporadic cavernomas. Furthermore, their results shed new light on the potential cell of origin of cerebral cavernous malformations that was previously considered to be of endothelial lineage. They have shown that it is in fact PGDS-positive pericytes that cause cavernomas in their models by disorganisation of the neurovascular unit.

Their results may provide a better understanding of the biology of sporadic cerebral cavernous malformations by highlighting the major role of PIK3CA mutations in them, rather than that of the CCM genes, initially considered to be predominant.

This result, which was corroborated by a preclinical model, opens new perspectives, still to be validated, for the development of targeted therapies for the treatment of sporadic human PIK3CA-mutated cavernomas that are refractory to surgery and radiotherapy or radiosurgery and lead to frequent complications. PIK3CA inhibitors have indeed shown promising results in patients with CLOVES syndrome (PIK3CA-related hypergrowth syndrome) as well as in patients with a wide range of tumours.

Sources

Matthieu Peyre, Danielle Miyagishima, Franck Bielle, Françoise Chapon, Michael Sierant, Quitterie Venot, Julie Lerond, Pauline Marijon, Samiya Abi-Jaoude, Tuan Le Van, Karim Labreche, Richard Houlston, Maxime Faisant, Stéphane Clémenceau, Anne-Laure Boch, Aurelien Nouet, Alexandre Carpentier, Julien Boetto, Angeliki Louvi,Michel Kalamarides, New England Journal of Medicine.

Our news on the subject

Le cortex moteur
Origin of Lance-Adams Syndrome Finally Elucidated
First described 60 years ago, chronic myoclonus following cerebral anoxia is now known as Lance-Adams syndrome. This is a severe disorder whose mechanisms were, until now, poorly understood. Geoffroy Vellieux, Vincent Navarro, and their colleagues at...
06.16.2025 Research, science & health
Tiré de New Theory of Colours de Mary Gartside, 1808
Aphantasia Might Be Linked to Alterations in Brain Connectivity
Thanks to 7T fMRI, researchers from Paris Brain Institute and NeuroSpin, the CEA's neuroimaging centre, are exploring the neural substrate of visual imagery at very high resolution for the first time. Their results, publiés [i] in Cortex, pave the...
06.06.2025 Research, science & health
Le développement du cerveau a une part d’aléatoire
The stochastic aspect of brain development
Although every person’s personality is the result of genetic and environmental factors, these are not the only factors at play. Bassem Hassan and his team at Paris Brain Institute have discovered that, in fruit flies (drosophila), individuality also...
05.12.2025 Research, science & health
Analyse MERSCOPE
New treatment pathways for brain malformation-linked focal epilepsy?
A study by Stéphanie Baulac’s team has revealed somatic mutations in different cell types in patients with type 2 focal cortical dysplasia. This disease causes drug-resistant epileptic seizures, for which the main treatment option is currently...
05.12.2025 Research, science & health
Un iceberg
The ICEBERG cohort, 10 years of collective scientific and medical mobilization
The ICEBERG cohort, initiated 10 years ago, is interested in studying factors predictive of the onset and progression of Parkinson’s disease.
05.15.2025 Research, science & health
La huntingtine est une protéine indispensable au développement embryonnaire, à la formation et au maintien du tissu cérébral.
Huntington's Disease: The Energy Hypothesis Gets Traction
Huntington's disease, a rare hereditary neurological disorder, is associated with an energy deficit that precedes the onset of symptoms and is closely linked to their progression. At Paris Brain Institute, Fanny Mochel and her colleagues are testing...
02.11.2025 Research, science & health
See all our news