Mapping uncharted territory: a gene expression signature for precision glioblastoma therapeutics.
Mapping uncharted territory: a gene expression signature for precision glioblastoma therapeutics.
复制标题
绘制未知领域：精准胶质母细胞瘤治疗的基因表达特征。
DOI：
10.1093/neuonc/noaa242
复制
发表时间：
2020
期刊：
影响因子：
15.9
通讯作者：
Miller,CRyan
中科院分区：
文献类型：
--
作者：
Skinner,KaseyR;Nabors,LBurt;Miller,CRyan
弥漫性胶质瘤是最常见的恶性原发性脑肿瘤，包括多种疾病。这些肿瘤的范围从较低级别的星形细胞瘤和少突胶质细胞瘤（II级和III级）到致命的胶质母细胞瘤（GBM，IV级），根据目前的世界卫生组织（WHO）分类进行诊断。1 GBM历来被视为一种单一的疾病的基础上的组织学标准;然而，分子技术的进步和下一代测序的出现已经揭示了显着的异质性内和肿瘤之间。1999年，NCI主任的挑战要求“科学界利用综合分子分析技术的力量，使肿瘤的分类更加信息化。作为回应，癌症基因组图谱（TCGA）和其他人确定了GBM中的突变驱动因素，并根据基因表达将肿瘤分类为亚型。肿瘤抑制因子如CDKN 2A、TP 53和PTEN以及包括EGFR在内的癌基因的改变是最常见的，描绘了这种疾病中常见的信号通路。此外，发现编码异柠檬酸脱氢酶（IDH 1或IDH 2）的基因中含有点突变的肿瘤与其IDH野生型（IDHwt）对应物的生存期更长相关。由于这些新发现的基因组改变及其对临床的影响，2016年WHO中枢神经系统肿瘤分类具有历史意义，因为它包括了诊断GBM的分子和组织学标准。1 IDH突变状态现在常规用于对GBM进行分类，用于疾病管理和临床试验招募。因此，根据基因组改变将GBM分为亚型对于合理的治疗设计和解释患者对治疗反应的变异性都是有用的。基于转录组特征的额外分层有希望
Diffusely invasive glioma, the most common and malignant primary brain tumor, comprises a diverse group of diseases. These tumors range from lower-grade astrocytomas and oligodendrogliomas (grades II and III) to the deadly glioblastoma (GBM, grade IV) when diagnosed based on the current World Health Organization (WHO) classification. 1 GBM has historically been treated as a single disease on the basis of histological criteria; however, advances in molecular technology and the advent of next-generation sequencing have revealed significant heterogeneity both within and among tumors. In 1999, the NCI Director’s Challenge asked “the scientific community to harness the power of comprehensive molecular analysis technologies to make the classification of tumors vastly more informative.” In response, The Cancer Genome Atlas (TCGA) and others identified mutational drivers in GBM and classified tumors into subtypes according to gene expression. Alterations in tumor suppressors such as CDKN2A, TP53, and PTEN and oncogenes including EGFR were among those most frequently found, delineating signaling pathways commonly affected in this disease. 2 Additionally, tumors harboring point mutations in the genes encoding isocitrate dehydrogenase (IDH1 or IDH2) were found to be associated with longer survival than their IDH wild-type (IDHwt) counterparts. 3 Because of these newly discovered genomic alterations and their implications for the clinic, the 2016 WHO classification of central nervous system tumors was historic in that it included both molecular and histological criteria for the diagnosis of GBM. 1IDH mutational status is now routinely used to classify GBM for both disease management and clinical trial enrollment. Thus, dividing GBM into subtypes according to genomic alterations is useful for both rational treatment design and explaining variability in patient response to therapy. Additional stratification based on transcriptome signatures holds promise
影响因子：
15.9
作者：
Johnson, Radia M.;Phillips, Heidi S.;Garcia, Josep
通讯作者：
Garcia, Josep
影响因子：
50.3
作者：
Verhaak RG;Hoadley KA;Purdom E;Wang V;Qi Y;Wilkerson MD;Miller CR;Ding L;Golub T;Mesirov JP;Alexe G;Lawrence M;O'Kelly M;Tamayo P;Weir BA;Gabriel S;Winckler W;Gupta S;Jakkula L;Feiler HS;Hodgson JG;James CD;Sarkaria JN;Brennan C;Kahn A;Spellman PT;Wilson RK;Speed TP;Gray JW;Meyerson M;Getz G;Perou CM;Hayes DN;Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network