Skip to main content

Or 34,00 After 66% tax deduction

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

GAB1, a good biomarker for Hedgehog-activated anterior skull base meningiomas

Published on: 14/06/2021 Reading time: 1 min
image

A study conducted by Julien Boetto and Franck Bielle (Sorbonne University. AP-HP) of the "Genetics and Development of Nervous System Tumours" team at the Paris Brain Institute highlights the potential of GAB1 as a new biomarker for Hedgehog-activated anterior skull base meningiomas. This discovery, published in Neuropathology and Applied Neurobiology opens the way to a better diagnosis of these tumours and the development of targeted therapeutic strategies.

Mutations activating the Hedgehog (Hh) signalling pathway have been described in anterior skull base meningiomas, raising hope for the use of targeted therapies. However, identification of Hh-activated tumours is hampered by the lack of a reliable immunohistochemical marker. Researchers report the evaluation of GAB1, an immunohistochemical marker used to detect Hh pathway activation in medulloblastoma, as a potential marker of Hh-activated meningiomas.

GAB1 staining was compared to SMO mutation detection with Sanger and NGS techniques as well as Hh pathway activation study through mRNA expression level analyses in a discovery set of 110 anterior skull base meningiomas and in a prospective validation set of 21 meningiomas.

Using an expression score ranging from 0 to 400, they show that a cut-off score of 250 lead to excellent detection of Hh pathway mutations (sensitivity 100%, specificity 86%). The prospective validation set confirmed the excellent negative predictive value of GAB1 to exclude Hedgehog independent meningiomas. The team describe a large series of 32 SMO-mutant meningiomas and define multiple ways of Hh activation, either through somatic mutations or associated with mutually co-exclusive SHH (Sonic Hedgehog) or IHH (Indian Hedgehog) overexpression independent of the mutations.

The assessment of GAB1 expression by an immunohistochemical score is a fast and cost-efficient tool to screen anterior skull base meningiomas for activation of the Hedgehog pathway. It could facilitate the identification of selected cases amenable to sequencing for hedgehog pathway genes as predictive markers for targeted therapy.

Sources

https://pubmed.ncbi.nlm.nih.gov/34056767/
Boetto J, Lerond J, Peyre M, Tran S, Marijon P, Kalamarides M, Bielle F. Neuropathol Appl Neurobiol. 2021 May 31

Our news on the subject

Interneurones. Crédit : UCLA Broad Stem Cell Research Center.
Stimulating specific neurons in the striatum stops compulsive behaviour
What if we could resist compulsions? These irrational behaviours, particularly common in obsessive-compulsive disorder (OCD), are hard to suppress. At Paris Brain Institute, Éric Burguière's team shows that we can anticipate them and block them ...
09.10.2024 Research, science & health
Les nerfs moteurs présents dans la moelle épinière se projettent vers la périphérie, où ils entrent en contact avec les muscles, formant des connexions appelées jonctions neuromusculaires. Crédit : James N. Sleigh.
Ultrasound show unexpected effects on motor neuron disease
Over the past fifteen years, neurosurgeons have been perfecting a fascinating technique: using ultrasound to temporarily open the blood-brain barrier to facilitate the action of therapeutic molecules in the central nervous system. At Paris Brain ...
09.05.2024 Research, science & health
Un neurone
Rett syndrome: a new gene therapy on the way
Gene therapy could be our best chance of treating Rett syndrome, a neurological disorder that causes severe intellectual and motor impairments. At Paris Brain Institute, Françoise Piguet and her colleagues have looked closely at brain cholesterol ...
07.16.2024 Research, science & health
Lésions d’un patient à l’inclusion dans le protocole (M0) disparues après 2 ans de traitement à la Leriglitazone (M24)
The dual effect of leriglitazone in X-linked Adrenoleukodystrophy (X-ALD)
In 2023, the team led by Professor Fanny Mochel (AP-HP, Sorbonne University), a Paris brain Institute researcher, showed that daily dose of leriglitazone slow down the progression of myelopathy in patients with X-linked adrenoleukodystrophy, and ...
06.28.2024 Research, science & health
Une tête de statue de l'île de Pâques sur laquelle sont posées des éléctrodes
A multimodal approach to better predict recovery in patients with disorders of consciousness
When a patient is admitted to intensive care due to a disorder of consciousness—such as a coma—establishing their neurological prognosis is a crucial yet challenging task. To reduce the uncertainty that precedes the medical decision, a group of ...
05.30.2024 Research, science & health
Population de bactéries commensales (en rouge) dans un intestin grêle de souris. Crédit : University of Chicago
The composition of the gut microbiota could influence decision-making
The way we make decisions in a social context can be explained by psychological, social, and political factors. But what if other forces were at work? Hilke Plassmann and her colleagues from the Paris Brain Institute and the University of Bonn show ...
05.16.2024 Research, science & health
See all our news