The importance of NF2 (neurofibromin 2), TRAF7 (tumor necrosis factor [TNF] receptor-associated factor 7), KLF4 (Kruppel-like factor 4), AKT1, SMO (smoothened), PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha), and POLR2 (RNA polymerase II subunit A) demonstrates that there are at least 6 distinct mutational classes of meningiomas.
Unilateral vestibular schwannoma and meningiomas in a patient with PIK3CA-related segmental overgrowth: Co-occurrence of mosaicism for 2 rare disorders.
We found a higher frequency of PIK3CA mutations [14/40 (35%) versus 18/530 (3%), P < 10-8] and TRAF7 mutations [16/40 (40%) versus 140/530 (26%), P < 0.001] and a lower frequency of NF2-related tumors compared with the control population of meningiomas [3/40 (7.5%) versus 169/530 (32%), P < 0.001].
Meningiomas frequently display activation of the PI3K/AKT/mTOR pathway, leading to elevated levels of phospho-eukaryotic translation initiation factor 4E binding proteins, which enhances protein synthesis; however, it is not known whether inhibition of protein translation is an effective treatment option for meningiomas.
Importantly, the discovery of clinically actionable alterations in a number of genes, including SMO, AKT1 and PIK3CA, has opened up novel potential avenues for therapeutic management of meningiomas.
In conclusion, we proposed that activation of PI3K/Akt and integrin-mediated signaling pathways was involved in the pathogenesis of benign and anaplastic meningiomas, respectively.
TAGLN2 can affect the proliferation, invasion and apoptosis of meningioma cells and may participate in the development of meningioma through regulating the PI3K/AKT signaling pathway.