胶质瘤基因突变笔记.ppt

Imaging genomic mapping in glioblastoma,Shen Xudong,Among adult central nervous system malignancies,glioblastoma(GBM) is the most common primary malignant brain tumor,accounting for 52% of all functional tissue brain tumor cases and 20% of all intracranial tumors.in the United States 在成人中枢神经系统恶性肿瘤中，胶质母细胞瘤（GBM）是最常见的原发性恶性肿瘤，占所有脑功能组织肿瘤的52%和所有颅内肿瘤的20%。,the best currently available multimodal treatment remains surgical resection followed by concomitant and adjuvant radiation therapy and temozolomide therapy. 目前GBM最合适的综合治疗仍然是手术切除后进行辅助放射治疗和替莫唑胺治疗。,despite recent advances in novel sequencing and microarray technologies that have led to profound discoveries and a better understanding of DNA-and RNA-based genomic alterations in cancer and the availability of these data to the scientific community, little progress in GBM therapy has been made 尽管新型测序和基因芯片技术的最新进展取得了重大发现和更好地理解DNA和RNA为基础的基因组在癌症中的改变和在科学界对这些数据的可用性，但胶质母细胞瘤的治疗取得的进展并不大。,The identification of microRNA (miRNA) and gene expression profiles in patients with distinct and clinically relevant tumor genotypes and phenotypes will uncover potential new therapeutic targets and molecular pathways,identify candidate patients for targeted therapy, predict a patients early response or failure to respond to therapy,and provide invaluable prognostic information. 患者微RNA、基因表达谱、临床相关的肿瘤基因型及表型的识别将发现潜在的新的治疗靶点和分子途径，识别候选病人进行有针对性的治疗, 预测病人的早期反应或失败响应治疗,并提供宝贵的预后信息。,The importance of epigenetics and changes in gene express, miRNA levels, and the surrounding tumor microenvironment is increasingly being recognized. 表观遗传学和基因表达的改变、miRNA水平及肿瘤周围微环境的重要性越来越被人们认识。,alterations in epigenetic processes can lead to genetic mutations, and genetic mutations in epigenetic regulators result in an altered epigenome. 表观遗传过程的改变可以导致基因突变，基因突变的表观遗传调节结果是基因组突变。,The prognostic and predictive values of the methylation status of the MGMT promoter and IDH status have shifted the GBM classification to a molecular-based classification that has clinical implications and relevance. MGMT启动子的甲基化状态和IDH突变状态的预后和预测值价值已经改变了胶质母细胞瘤的分类至分子水平，具有临床意义和相关性。,However, as of yet, no molecular profiling based GBM classification has sufficiently high clinical relevance for the selection of different therapeutic strategies and the determination of patient outcome. 然而，迄今为止，在针对不同的治疗策略的选择和患者预后的判断方面，还没有基于分子基础的GBM的分类。,Hypermethylation of the MGMT promoter causes epigenetic-mediated silencing of MGMT and has been confirmed in multiple clinical trials as an important predictive genomic biomarker in the context of alkylating agents such as temozolomide. it is also one of the most important prognostic factors for progression-free survival and overall survival in patients with GBM. IDH1 mutations can help differentiate primary from secondary GBMs and portend a better prognosis in patients who harbor these mutations.,MGMT启动