Genome Analysis Of Brain Tumors In Siblings And Establishment And Application Of An Immunocompetent Glioma Mouse Model

Through decades of research progress,central nervous system tumors(CNS Tumors)remain the most lethal of all tumors.Glioma and medulloblastoma are two of these typical lethal tumors.Currently,the common treatments are surgery and chemoradiotherapy.However,many of these tumors are not completely resectable.Furthermore,they can become resistant to chemoradiotherapy,with the presence of tumor stem cells.Various immunotherapies for brain tumors are also advancing.However,the survival of patients with brain tumors has not been significantly prolonged.To a large extent,the reason is that we know very little about the immune microenvironment of brain tumors.Therefore,exploring the immune environment of brain tumors remains one of the bases and keys to therapy.In addition,next-generation sequencing technology,which also means high-throughput sequencing,has developed rapidly in the last decade and has been frequently applied in scientific research and clinical fields.It provides an effective platform for us to study brain tumors in depth.In this paper,we introduce the characteristics and current research results of CNS tumors,especially medulloblastomas and gliomas including glioma stem cells and immunocompetent murine glioma models,as well as the basic principles,development and applications of next-generation sequencing technologies.In this paper,we analyzed the gene mutations in familial childhood brain tumor cases including glioma and medulloblastoma by genome sequencing.The sequencing result revealed that the somatic mutations in the two cases were much more than those in most tumor cases,which was a result of mutations in MSH6,a gene related to DNA mismatch repair.For such a phenomenon,the immune checkpoint inhibitor PD1 antibody might have a therapeutic effect.At the same time,we realized that the study of immunotherapy and intracranial immune microenvironment is important for brain tumor therapy.We then established an immune-competent murine glioma model through CRISPR gene-editing technology and brain stereotactic transplantation technology.Validation and application of the established model were followed.This model provided a new effective platform for immunotherapy evaluation and a novel model for brain immune microenvironment research.