Comprehensive analysis of molecular and clinical characteristics of 1000 children with low-grade glioma.

Children with low-grade gliomas (pLGG) are children with a common brain tumor, accounting for about 30%Unlike adult symitomas, which occur primarily in the hemisphere of the brain and inevitably turn into high-level gliomas, pLGG can occur throughout the central nervous system and have little transformationHowever, the prognosis and treatment response scants highlyMolecular spectroscopy studies over the past decade have shown that pLGG is usually driven by genetic changes in the RAS/syrotheal activated protein kinase (RAS/MAPK) pathway, most commonly involving changes in BRAF or reproductive NF1 somatic cellsIn addition, rare non-RAS/MAPK changes affecting RAS/MAPK signal transduction have been reportedSo far, some key issues have not been resolved: (1) Are all NF1, BRAF fusion and BRAF mutant tumors the same? (2) What is the mechanism of pLGG, which has not been found to have genetic changes? (3) What are the clinical characteristics of the rare changes of pLGG? Is its return unique? 4 Does detecting molecular changes help to provide a biological basis for disease stratification? The study, conducted by Cynthia Hawkins of the Department of Pathology at Children's Hospital toronto and The Department of Experimental Medicine and Pathology at the University of Toronto, used comprehensive clinical data to describe the molecular characteristics of 1,000 pLGG patients, including the rarest pLGG molecular entities and their clinical characteristics, published in Cancer Cell in April 2020research methodsincluded in the study of 19-year-old pLGG pediatric patients treated and followed at Children's Hospital Toronto, Canada, from 1986 to 2017Tumors are evenly distributed across the brain and hemisphereofthe, while tumors that are located solely in the brain stem, spinal cord and widespread spread are rareThe age of diagnosis of the tumor is 0-18.7 years, with an average age of 7.6 years, and the age of diagnosis of pLGG in the hemisphere of the brain is later than in other parts of the brain (p 0.0001)There were significant differences in tumor site, progression-free survival (PFS) and total survival (OS) (p.0001)Thirty-three percent of patients had tumor progression, but only 7.5 percent died from pLGGin the study, NF1-driven pLGG accounted for 14%Compared to optic glioma (optic pathway glioma, OPG), OS and PFS are significantly worse in patients with NF1-driven tumors that occur off-roadIn addition, in high-risk, relapsed or biopsy NF1-driven pLGG, 20% of other molecular drivers have mutations, including BRAF p.V600E, FGFR1 and/or H3F3A (H3.3) p.K27MStudies have shown that non-OPG NF1-driven tumors require special treatment, including early biopsy and molecular analysisNotably, KIAA1549-BRAF, BRAF p.V600E and reproductive NF1 mutations accounted for 68% of tumors Another 17% of cases were rare In 84% of pLGG cases, there was a driven mutation, excluding molecular change in NF1 patients the results of the study the researchers used different means such as RNA sequencing to verify whether 16% of the undetected mutation of pLGG caused the RAS/MAPK pathway to increase; researchers further collected data on 61 cases of children, combining clinical and molecular information to study which characteristics could predict the clinical prognosis of pLGG It was found that patient prognosis was significantly correlated with changed types, such as rearrangement drives or SNV drivers, but not entirely related to specific genetic changes Re-run-driven pLGG patients had good long-term prognosis, fewer deaths and less progression , there was a significant difference in mortality rates between SNV-driven pLGG patients and re-arrangement drivers (p.0001), and significant differences compared to fusion drivers in tumor progression (p.0001) In addition, patients with re-scheduled-driven pLGG diagnosis are younger (median 6.6:10.9 years; p 0.0001) and are rich in WHO I-level histological characteristics (p.0001) the researchers defined the risk stratification of pLGG: pLGG with gene fusion or reproductive NF1 mutation swells into the low-risk group; BRAF p.V600E, FGFR1 SNV, IDH1 p.R132H or MET mutation without CDKN2A deficiency Tumors formed a medium-risk group; H3.3 p.K.27M or BRAF p.V.V600E with CDKN2A deficiency group) formed a high-risk group, and finally, the undetermined pLGG trends showed that PFS and OS trends were consistent with the risk of low-risk groups and the risk group Conclusions results show that 84% of pLGG has driven changes, KIAA1549-BRAF, BRAF p.V.V600E and NF1 mutations account for 2/3 of pLGG, and pLGG, which has not been detected, often shows RAS/MAPK path increase, i.e THE RAS/MAPK pathway is almost universally activated in pLGG Depending on the type of pLGG change, i.e the rearrangement drive or SNV drive change can be roughly classified Compared with SNV-driven pLGG, patients with resection-driven tumor diagnosis were younger, had whoatoic histological characteristics, were slow in tumor progress, and had a low mortality rate PLGG can be broken down into different risk categories based on clinical-molecular correlation Risk-based stratification can effectively predict patient prognosis The above research data highlight the biological and clinical differences between pLGG subtypes and open up new avenues for improving future treatments Finally, the authors note that the information provided in this study helps to group pLGG snout snrituated different progression-free and total survival periods, and may require different diagnostic options and treatments for different risk groups; 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