Clinical Application of Meningioma Genomics Research

Michael Karsy, of the Center for Clinical Neuroscience at the University of Utah, and others reviewed recent advances in meningioma genomics to explore their relevance to clinical practice, which was published in Neurosurgical Focus in June 2018- From the article.Neurosurg Focus.2018 Jun;44 (6): E10doi: 10.3171/2018.2.FOCUS1849.
meningioma is a common intracranial tumor, accounting for 36% of brain tumorsRecently, an endocoma genomics study analyzed the pathological basis of meningioma from the genetic level and found that genes such as NF2, TRAF7, KLF4, AKT1, SMO, PIK3CA and POLR2 played an important role in the distribution of meningioma (Figure 1), and revealed that there were at least 6 different types of meningioma mutations and 6 types of methylationCompared with the traditional WHO grade, the methylation of meningioma can significantly improve the predicted prognosisMichael Karsy, of the Center for Clinical Neuroscience at the University of Utah, and others reviewed recent advances in meningioma genomics to explore their relevance to clinical practice, which was published in Neurosurgical Focus in June 2018Figure 1The common genetic variations of meningiomas and the good hair of tumorsthe authors searched PubMed for 58 and 10 studies, using the words "meningioma and genomics" and "meningioma and whole genome chips"After referring to the Preferred Reporting Project (PRISMA) Statement for System Evaluation and Analysis (http://prisma-state.org/), identify reviews of six key papersThe authors collected 24 reports on meningioma in clinical studies (clinicaltrials.gov) that recruited patients with meningioma2016 WHEN WHO updated the central nervous system tumor classification, it emphasized the importance of tumor gene mutations in determining the subtype of meningioma histologicalIn 50%-60% of meningioma patients, the loss of neurofibromatoprotein 2 (NF-2) was found, and in 40%-80% of the pericoid meningioma, the loss of chromosome 22 in which NF2 is located was found NF2 is a cell membrane binding protein that regulates participation in cell armature remodeling, cell-cell adhesion, and cell migration The absence of NF2 activates a variety of carcinogenic pathways, including the Ras/Pro-split activated protein kinase pathway, the Notch pathway, the phosphate inositol kinase 3 (PI3K)/AKT Hippo pathway, the hippo path, and the mTOR pathway (the target of rapamycin) Clark et al found in early studies that there were a range of other mutations in meningiomas with non-NF2 mutations, namely TRAF7, KLF4, AKT1, and SMO mutations Brastianos et al confirmed AKT1 and SMO mutations in meningioma Abedalthagafi and others compared genome hybridization of 150 meningiomas and found that PIK3CA mutations were present in 7% non-NF2 mutant meningioma Follow-up studies such as Clark and others have revealed the importance of mutations such as POLR2A in the course of meningioma All of the above studies suggest that the origin of meningioma may have come from early progenitor cells or tumor stem cells Immune-driven methods, immunomodulators or pan-targeted therapies may be effective than single-target therapy (Table 1) Study of Genomics found key genes for meningioma Sahm and others analyzed DNA methylation in 497 meningiomas and DNA methylation of 309 tumors growing outside the skull, identifying six clinically different subgroups The DNA methylated subgroup was more accurate lysed than WHO in predicting clinical progress According to the RESULTS of DNA methylation, meningioma can be divided into methylation benign categories 1-3, methylation intermediate categories A and B, and methylation malignant categories Recurrent tumors maintain the same methylation pattern Kaplan-Meier's survival curve found that methylation subgroups predicted patients' survival more accurately than WHO ratings (Figure 2) figure 2 Key signaling pathways for the onset of meningocomy the results of genomics studies that have changed the understanding of meningiomas However, these results have not yet been applied to the clinical, still remain in the research stage, and have not changed the surgical procedure The current surgical principle is still to remove the tumor to the maximum extent, while protecting the neurovascular structure clinical trials based on meningioma genomics aim to improve treatment outcomes through targeted mutations Currently, patients with recurrent or progressive meningiomas are being recruited to screen for AKT1, SMO or NF2 mutations, as well as to treat effects with AKT, SMO, and FAK inhibitors (NCT02523014) SMO inhibitors, known as vismodegib, have been approved for the treatment of base cell carcinoma and are currently being tested for meningioma with SMO mutations (NCT02523014) Dual mTORC1 and mTORC2 inhibitors (AZD2014) (NCT03071874 and NCT02831257) and BRAF inhibitors nivolumab (NCT02648997 and NCT03173950) began to enter the meningioma treatment trial Immunomodulation therapy, such as PD-L1 inhibitor pembrolizumab, is also being tested (NCT03279692) , genomics research reveals a new understanding of the mechanism of meningioma development, and confirms the importance of mutations such as NF2, TRAF7, KLF4, AKT1, SMO, PI3KCA and POLR2A in the development of meningioma Six unique methylation sub-classes have a better predictive prognosis than traditional WHO grades Current clinical trials are using genomic subclass information for precision treatment.