Advances in the study of adult diffuse glioma

Around 100,000 people worldwide are diagnosed with diffuse glioma each year; The most deadly glioblastomas accounted for 70-75% of diffuse gliomas, with a median lifetime of 14-17 monthsIn 2007, WHO classified diffuse gliomas only on the criteria of tumor histologyIn the past ten years, the study of tumor molecular science has provided new insights into the complex genetic mechanisms, chromosomes and epigenetic changes of glioma formation and developmentAs a result, in 2016 WHO introduced a new classification system based on tumor morphology and molecular changesAnnette MMolinaro, of the Department of Neurosurgery and Epidemiological Biostatistics at the University of California, San Francisco, and annette MMolinaro, among others, reviewed the progress of a decade of research on glioma classification, clinical and genetics, and other risk factors, and published online June 2019 in Nat Revthe results of the study
the 2007 WHO guidelines for the classification of gliomaweres are based on histology criteria, so the heterogeneity between observers is very large, and the survival rate of patients in the same grade is also very different2016, WHO integrated tumor morphology, IDH mutation and 1p19q total deletion into the new classification system for adult diffuse gliomas, which were divided into five main types:(1) glioblastoma, IDH wild;(2) glioblastoma, IDH mutant type;(3) diffuse or interdessanomic atomtumor, IDH wild;(4) diffuse or mesomorphic adenoid atomoma, IDH mutant;(5) less protrusive glioblastoma or interstitial degenerative glioblastoma, IDH mutant type and 1p19q total missingthe new system is particularly important in two ways:no longer treats less protrusive cell tumors as a separate entity; , by contrast, through the IDH mutation and 1p19q co-missing state, reflects the genetic characteristics of 1p19q complete astrocyma or 1p19q commonly missing less protogloomas When histology is inconsistent with molecular characteristics, molecular characteristics become the main determinant stakes in classification the new system describes the age of diagnosis and prognosis more accurately The 7th type of new type is mid-line diffuse glioma, H3K27M mutant type, mainly in patients with small age of onset, tumor situated in the middle-line area of the spinal cord, thalamus, brain stem and cerebellum, the histology classification of tumor is usually lower, but its clinical results are poor other tumor markers not adopted by the WHO's tumor classification system in 2016 are also used to fine-tune the prognosis of certain types of gliomas numerous studies have shown the importance of telomere-sustaining genes, including TERT and ATRX mutations, to classification and prognosis different DNA methylation characteristics are associated with the prognosis of gliomas using methylation and gene expression analysis found that six different panglioma DNA methylation and transcriptome subtypes, known as LGM1-LGM6 DNA-based methylation classification is used to avoid heterogeneity between observers, thereby improving diagnostic accuracy DNA damage caused by tamoxamine can be repaired by methylated DNA-protein cysteine methyl transferase (MGMT) The importance of MGMT initiatormethylation as a prognostic biomarker has been proven in several clinical trials and studies distortion that affects the signaling pathways of cell cycles is a common mechanism of cell growth loss, which is most commonly manifested in glioblastoma as a puricosm loss (50-60%) of CDKn2a and/or CDKn2b, and has now been identified as an independent marker of poor prognosis of IDH mutant astrocyte tumors (including glioblastoma) Globally, the incidence of diffuse glioma in adults varies widely age-adjusted population of over 40 years of age, the annual incidence of age-adjusted astrocyma was 6.8 cases per 100,000 people the population of the Nordic-dominated countries, from 7.8 in the United States to 9.6 in Australia and New Zealand, higher than the population of Countries with a predominantly Asian or African population, from 1.9 in South-East Asia to 3.3 in India future studies will help to understand these differences by comparing genetic, environmental and regional lifestyle risk factors within and between countries most population-based studies have shown that, in addition to geographic differences, the incidence of glioma varies by age, sex, race, and tumor histology (or WHO 2016 subtype), and the survival rate of glioma patients varies by age, sex, and tumor subtype the incidence of astrocyma increases with age and peaks between the ages of 75 and 84 the incidence of men is 40-50 per cent higher than for women in all age groups from 2000 to 2014, the 1- and 5-year relative survival rates for adult glioblastoma were 41% and 5%, respectively, and the 1- and 5-year relative survival rates for patients with non-glioblastoma were 72% and 44%, respectively this age pattern may be related to the time required for multiple genetic changes to achieve malignant transformation other factors associated with survival rates, such as tumor removal, Karnowski performance score, and treatment 5% to 10% of glioma patients without a family history of cancer syndrome have a family history of glioma compared to glioma patients with out-of-class relatives, patients with first-degree relatives had a twice the risk of developing primary brain tumours on chain analysis, all-exon sequencing, and whole genome association studies (GWAS) are ongoing to raise awareness of what species variants may increase the risk of glioma a large GWAS study has verified that 25 single nucleotide polymorphisms (SNPs) are closely related to the risk of glioma in adults , 11 SNPs were associated with the risk of glioblastoma, 19 SNPs were associated with the risk of non-glioblastoma, and the strongest relative risk was 8q24.21 variation, which could increase the relative risk of star-like cytoma, IDH mutation or less prosyma by more than 6 times there are few identified non-genetic risk factors for the occurrence of diffuse gliomain in adults only considerionitoe ionizing radiation is the cause of glioma, but only in only a few cases ionizing radiation damagedna, and tumors appear within 7-9 years of exposure ionizing radiation is dose-dependent on the risk of diffuse gliomas, and low-dose ionizing radiation (e.g atomic bomb survivors) and high-dose ionizing radiation (e.g radiotherapy for childhood cancer) increase the risk of glioma many studies have shown that allergy history or other specific diseases, such as hay fever, eczema and asthma, are associated with a lower incidence of glioma, and that the risk of glioma is significantly reduced in people with history of allergy is due to the conversion of a specific state to enhance immune surveillance, thereby suppressing tumor growth in the early stages also believe that an overactive immune system can remove potential environmental toxins the importance of changes in immune cells affecting the prognosis of tumor patients is being studied and will be of great significance to the development of immunotherapy conclusions concluded that the results of the past 15 years have laid a solid foundation for revealing the molecular pathways and genetic risks of gliomas, as well as future research directions Integrating molecular data into who's 2016 pervasive glioma classification system is critical to developing treatment options and improving predictive prognosis In the future, it is necessary to strengthen research in understanding the interaction of genetic and non-genetic risk factors in the formation of gliomas and to identify mutations within specific molecular subtypes of adult diffuse gliomas In addition, the role of the patient's immune state in the various stages of glioma formation has yet to be clarified To address these critical issues, future research will require greater international cooperation and the establishment of large databases, including clinical results and imaging data.