Micro-evolution trajectory of glioma recurrence

Diffuse glioma is the most common malignant brain tumor in adults, and it is still inevitable to relapse after surgical removal and chemotherapyMolecular diagnosis of gliomas has been widely used, but new changes in the genetic characteristics of gliomas over time and after treatment are not clearFloris PBarthel of the Jackson Genomics Laboratory in the United States, among others, analyzed three glioma subtypes, (1) IDH mutation alconal co-missing chromosome1p/19q, (2) non-chromosome 1p/19q common missing NE mutation and (3) IDH wild type of longitudinal molecular change characteristics, published in the December 2019 journal Naturethe results of the study
the researchers combined data from 222 adult patients with recurrent gliomas in 35 hospitals, analyzed sequencing data and matching clinical data on primary and recurrent tumors, and found that the incidence of initial tumor mutations was consistent with previous reports, excluding 35 cases of ultra-high mutations of more than 10 mutations/million base (Mb), and the incidence of 70% of recurrent tumor mutations increasedThe mutation was divided into the initial mutation, the recurrence mutation and the initial and relapse of the common mutationIt was observed that the longer the tumor progression, the more significant the incidence of tumor mutation son rose (P-0.0043)the prefanizers used in the treatment of gliomascan induce ultra-high mutations, while the incidence of 3 glioma subtypes is significantly different (Fisher precision test P 2.0 x 10-3)Treatment-induced super-high mutations were associated with disease progression, but there was no difference in total survival rates between chemotherapy-induced hypermutants and non-super-mutation strains, and were not related to age, tumor subtype and MGMT methylationmicroenvironment and various treatments can induce changes in the structure of the driving gene clones when the tumor recurs, but analyzing the three main subtypes of glioma mutations and copy numbers found that the driving genes detected early in the tumor's occurrence still exist edgy genes at the time of recurrenceIn the course of tumor progression, there were similarity in the cloned structure (Kendall rank correlation, tau s 0.20; P 3.76 x 10-24), and no specific gene modification severance in the event of recurrence was found A full assessment of genetic changes in initial and recurrent tumors shows that the most important driving gene changes occur in the early stages of glioma study whether radiotherapy and chemotherapy can produce genetic mutation effects, no significant correlation between subclonal structure and radiation and chemotherapy was observed (Fisher precision test P.05), indicating that the current standard treatment of glioma has limited effect on subclonstructure mutations often lead to the emergence of new antigens, and the immune system can attack these immune-derived tumor cells, and the sub-clone structure that chooses to evade the immune response may have an advantage conclusion
comprehensive lysing shows that the treatment-induced super-mutation can occur in various subtypes of glioma, but has little effect on the overall survival of patients, so the clinical importance of glioma super-mutation is questioned At the same time, the study found that immuno-editing activity did not change over time in gliomas The most important driving gene changes occur early in the onset of glioma, meaning that current clinical glioma treatments are largely random.