文章：

胶质母细胞瘤G1-G7分子亚组分类向临床实践的转化：全面的人口统计学与分子通路特征分析

Translation into Clinical Practice of the G1-G7 Molecular Subgroup Classification of Glioblastoma: Comprehensive Demographic and Molecular Pathway Profiling

原文发布日期：15 January 2024

DOI: 10.3390/cancers16020361

类型: Article

开放获取: 是

英文摘要：

Glioblastoma is the most frequent and malignant primary neoplasm of the central nervous system. In a recent breakthrough study on a prospective Discovery cohort, I proposed the first all-inclusive molecular classification of glioblastoma into seven subgroups, G1-G7, based on MAPK pathway activation. New data from a WHO-grade-4 diffuse glioma prospective Validation cohort offers, in this study, an integrated demographic–molecular analysis of a 213-patient Combined cohort. Despite cohort differences in the median age and molecular subgroup distribution, all the prospectively-acquired cases from the Validation cohort mapped into one of the G1-G7 subgroups defined in the Discovery cohort. A younger age of onset, higher tumor mutation burden and expanded G1/EGFR-mutant and G3/NF1 glioblastoma subgroups characterized the glioblastomas from African American/Black relative to Caucasian/White patients. The three largest molecular subgroups were G1/EGFR, G3/NF1 and G7/Other. The fourth largest subgroup, G6/Multi-RTK, was detailed by describing a novel gene fusionST7–MET, rarePTPRZ1–MET,LMNA–NTRK1andGOPC–ROS1fusions and their overexpression mechanisms in glioblastoma. The correlations between the MAPK pathway G1-G7 subgroups and the PI3-kinase/PTEN, TERT, cell cycle G1 phase and p53 pathways defined characteristic subgroup pathway profiles amenable to personalized targeted therapy. This analysis validated the first all-inclusive molecular classification of glioblastoma, showed significant demographic and molecular differences between subgroups, and provided the first ethnic molecular comparison of glioblastoma.

摘要翻译： 

胶质母细胞瘤是中枢神经系统中最常见且恶性程度最高的原发性肿瘤。在一项针对前瞻性发现队列的最新突破性研究中，我基于MAPK通路激活首次提出了将胶质母细胞瘤全面划分为七个亚组（G1-G7）的分子分类体系。本研究通过WHO 4级弥漫性胶质瘤前瞻性验证队列的新数据，对包含213例患者的综合队列进行了人口学-分子整合分析。尽管两个队列在中位年龄和分子亚组分布上存在差异，但验证队列中所有前瞻性收集的病例均能对应到发现队列定义的G1-G7亚组之一。与非裔/黑人患者相比，高加索/白人患者的胶质母细胞瘤具有发病年龄更轻、肿瘤突变负荷更高以及G1/EGFR突变型和G3/NF1亚型比例扩增的特征。三个最大的分子亚组分别为G1/EGFR、G3/NF1和G7/其他。第四大亚组G6/多RTK型通过描述新型基因融合ST7-MET、罕见融合PTPRZ1-MET、LMNA-NTRK1和GOPC-ROS1及其在胶质母细胞瘤中的过表达机制得到详细阐释。MAPK通路G1-G7亚组与PI3激酶/PTEN、TERT、细胞周期G1期及p53通路之间的相关性，定义了适用于个体化靶向治疗的特征性亚组通路谱。该分析验证了首个全面性胶质母细胞瘤分子分类体系，揭示了亚组间显著的人口学和分子差异，并首次提供了胶质母细胞瘤的种族分子比较数据。

原文链接：

Translation into Clinical Practice of the G1-G7 Molecular Subgroup Classification of Glioblastoma: Comprehensive Demographic and Molecular Pathway Profiling