To investigate neurofibromatosis type 2 (NF2) gene mutation at mRNA levels in sporadic orbitocranial meningioma and its association with progesterone receptor (PR) mRNA expression.
Next-generation sequencing studies and increasingly sophisticated <i>NF2</i>-deletion-based <i>in vitro</i> and <i>in vivo</i> models have helped elucidate the consequences of merlin loss in meningioma pathogenesis.
Meningiomas are more common in females and 70-80% express the progesterone receptor, raising the possibility that high-dose exogenous estrogen/progesterone exposure, such as occurs during fertility treatments, may increase the risk of developing a meningioma.
The WHO grade (2007 classification), Ki67-MIB1, progesterone receptor expression, and histological subtype were reexamined and correlated to the meningioma location, classified as medial skull base, lateral skull base, non-skull base, and spinal.
The best defined of these syndromes is neurofibromatosis type 2, which is caused by a mutation in the NF2 gene and has a meningioma incidence of approximately 50%.
In two pairs of syngenous meningeal or meningioma cell lines with or without shRNA-mediated knockdown of NF2/Merlin a nearly complete loss of CD73 mRNA expression was observed after the knockdown (p ≤ 0.001).
Significant association between lower expression of PR (OR 11.7; 95% CI 4.17-32.9; <i>P</i> < 0.001 comparing the lowest quartile vs. 3 highest quartile of PR) and <i>NF2</i> (OR 4.23; 95% CI 1.85-9.67; <i>P</i> = 0.001 comparing the 2 lowest quartiles vs. 2 highest quartiles) with increased risk of meningioma were also reported.
We identified over 2000 proteins in comparative experiments between Merlin-deficient schwannoma and meningioma compared to human Schwann and meningeal cells respectively.
Methylation-specific PCR verified that IL-1β induced methylation of the NF2 promoter and decreased NF2/merlin expression in meningioma/leptomeningeal cells.
Merlin expression and YAP phosphorylation were also affected by cell density in the IOMM-Lee and HKBMM human meningioma cell lines; nuclear localization of YAP was regulated by cell density and extracellular matrix (ECM) stiffness in IOMM-Lee cells.
This study explores the status of the NF2 gene in pleuropulmonary meningothelial proliferations compared with CNS meningioma using interphase fluorescence in situ hybridization.
Moreover, Axl positively regulates the oncogene Yes-associated protein, which is known to be under merlin regulation in schwannoma and is involved in increased proliferation of merlin-deficient meningioma and mesothelioma.
EGFR expression and Ki67 LI correlated with grade of meningioma P < 0.0001 and P < 0.0001 respectively which were statistically significant whereas p53 expression did not correlate (P - 0.90).
Cell lines Ben-Men-1 (benign), IOMM-Lee and KT21 (malignant), and pairs of merlin-positive or -negative meningioma cells were used to assess sensitivity toward mTORC1 inhibitors in methyl-tetrazolium and bromodeoxyuridine (BrdUrd) assays.