Molecular Genetics of Intracranial Meningiomas with Emphasis on Canonical Wnt Signalling

Abstract

Research over the last decade recognized the importance of novel molecular pathways in pathogenesis of intracranial meningiomas. In this review, we focus on human brain tumours meningiomas and the involvement of Wnt signalling pathway genes and proteins in this common brain tumour, describing their known functional effects. Meningiomas originate from the meningeal layers of the brain and the spinal cord. Most meningiomas have benign clinical behaviour and are classified as grade I by World Health Organization (WHO). However, up to 20% histologically classified as atypical (grade II) or anaplastic (grade III) are associated with higher recurrent rate and have overall less favourable clinical outcome. Recently, there is emerging evidence that multiple signalling pathways including Wnt pathway contribute to the formation and growth of meningiomas. In the review we present the synopsis on meningioma histopathology and genetics and discuss our research regarding Wnt in meningioma. Epithelial-to-mesenchymal transition, a process in which Wnt signalling plays an important role, is shortly discussed.

HbA1c in patients with intracranial meningiomas WHO grades I and II: A preliminary study

“…Several risk factors for meningiomas have been reported, with ionizing radiation, hypertension, and female sex hormones, showing a possible positive correlation. Much is known about the genetics of meningiomas as well. The effects of various aspects of the metabolic syndrome, primarily glucose metabolism and diabetes, have also been investigated fairly extensively in relation to meningioma risk .…”

Molecular Mechanism and Approach in Progression of Meningioma

“…The most common chromosomal abnormality in meningioma is in chromosome 22, observed in 40–70% of grade I meningioma. Beyond the loss of chromosome 22, few other chromosomal abnormalities have been observed in benign meningioma ( 10 ). In an analysis of chromosome 22 in 44 sporadic meningiomas, researchers found that in 43 cases, all or part of the chromosome had been deleted, the majority of deletions occurring in the neurofibromatosis type 2 (NF2) region, suggesting that the mutation on NF2 leads to the occurrence of meningioma ( 11 ).…”

“…E-cadherin (encoded by CDH1 at 16q22.1) is a calcium-dependent adhesion molecule, mediating their interaction with epithelial cells ( 40 ). It relies on β-catenin to play a role in cell adhesion, which is considered an indirect regulator of the Wnt signaling pathway ( 10 ). E-cadherin and β-catenin comprise the E-cadherin/catenin complex that regulates cell adhesion and maintains cell polarity and stability ( 40 ).…”

Skull base invasive low-grade meningiomas, a distinct genetic subgroup: A microarray gene expression profile analysis

“…Meningioma was not an exception; in the last two-decade several papers were published regarding methods and reviews of the molecular biological profile of meningiomas [2,4,5,22,23,33,38,43,47,49]. The efforts of some of these studies helped in identifying unique molecular expression correlated with the WHO grades.…”