背景:随着分类的重大转变,风险分层,和神经胶质瘤的护理标准,我们试图了解这些肿瘤患者的总体生存率如何受到分子特征的影响,临床指标,和接受的治疗。
方法:我们从癌症基因组图谱中收集了一组组织病理学诊断为神经胶质瘤的患者,基因组学项目证据瘤形成信息交换,和达纳-法伯癌症研究所/布莱根妇女医院。这纳入了回顾性临床,组织学,和分子数据以及对患者生存的前瞻性评估。
结果:确定了4,400个胶质瘤:2,195个胶质母细胞瘤,1,198IDH1/2-突变型星形细胞瘤,531少突胶质细胞瘤,271其他IDH1/2野生型神经胶质瘤,和205个小儿型神经胶质瘤。分子分类更新了27.2%的神经胶质瘤的原始组织病理学诊断。检查神经胶质瘤亚型之间分子改变的分布揭示了致瘤途径中相互排斥的改变。与TCGA患者相比,非TCGA患者的总生存率显着提高,26.7%,55.6%,胶质母细胞瘤的生存期延长127.8%,IDH1/2-突变型星形细胞瘤,和少突胶质细胞瘤(均p<0.01)。几个预后特征被表征,包括胶质母细胞瘤的NF1改变和21q丢失,IDH1/2突变型星形细胞瘤的EGFR扩增和22q丢失。利用这个群体的规模,生成列线图以评估基于患者年龄的总体生存概率,肿瘤的分子特征,以及所接受的治疗。
结论:通过应用现代分子标准,我们描述了神经胶质瘤亚型的基因组多样性,确定临床适用的预后特征,并提供有关患者生存的最新信息,以作为正在进行的调查的参考。
BACKGROUND: With the significant shift in the classification, risk stratification, and standards of care for gliomas, we sought to understand how the overall survival of patients with these tumors is impacted by molecular features, clinical metrics, and treatment received.
METHODS: We assembled a cohort of patients with a histopathologically diagnosed glioma from The Cancer Genome Atlas, Project Genomics Evidence Neoplasia Information Exchange, and Dana-Farber Cancer Institute/Brigham and Women\'s Hospital. This incorporated retrospective clinical, histological, and molecular data alongside prospective assessment of patient survival.
RESULTS: 4,400 gliomas were identified: 2,195 glioblastoma, 1,198 IDH1/2-mutant astrocytoma, 531 oligodendroglioma, 271 other IDH1/2-wildtype glioma, and 205 pediatric-type glioma. Molecular classification updated 27.2% of gliomas from their original histopathologic diagnosis. Examining the distribution of molecular alterations across glioma subtypes revealed mutually exclusive alterations within tumorigenic pathways. Non-TCGA patients had significantly improved overall survival compared to TCGA patients, with 26.7%, 55.6%, and 127.8% longer survival for glioblastoma, IDH1/2-mutant astrocytoma, and oligodendroglioma respectively (all p<0.01). Several prognostic features were characterized, including NF1 alteration and 21q loss in glioblastoma, and EGFR amplification and 22q loss in IDH1/2-mutant astrocytoma. Leveraging the size of this cohort, nomograms were generated to assess the probability of overall survival based on patient age, the molecular features of a tumor, and the treatment received.
CONCLUSIONS: By applying modern molecular criteria, we characterize the genomic diversity across glioma subtypes, identify clinically applicable prognostic features, and provide a contemporary update on patient survival to serve as a reference for ongoing investigations.