1000例儿童低级别胶质瘤的分子生物学及临床分析

作者：王韵壹、李英、熊慧卿

本期文章：《癌细胞》：Volume 37 Issue 4

加拿大多伦多大学病童医院Cynthia Hawkins研究组的一项最新工作，报道了1000例儿童低级别胶质瘤的分子和临床综合分析。2020年4月13日，国际知名学术期刊《癌细胞》发表了这一成果。

研究人员表示，儿童低级别神经胶质瘤（pLGG）通常是由RAS促丝裂原激活蛋白激酶（RAS/MAPK）途径的遗传改变驱动的，但其临床结局显示出无法解释的变异性。

为了解决这个问题，研究人员对一组1000余个临床注释的pLGG进行了表征。84％的病例具有驱动程序改变，而那些未发现改变的病例也经常表现出RAS/MAPK通路的上调。pLGG可以根据其改变类型大致分类。与SNV驱动的肿瘤相比，重排驱动的肿瘤在更早年龄段被诊断出，且具有WHO I级组织学特征，其进展缓慢，很少导致死亡。

临床分子的进一步亚分类将分层的pLGG划分为风险类别。这些数据突出了pLGG亚型之间的生物学和临床差异，并为将来的治疗改进开辟了道路。

附：英文原文

Title: Integrated Molecular and Clinical Analysis of 1,000 Pediatric Low-Grade Gliomas

Author: Scott Ryall, Michal Zapotocky, Kohei Fukuoka, Liana Nobre, Ana Guerreiro Stucklin, Julie Bennett, Robert Siddaway, Christopher Li, Sanja Pajovic, Anthony Arnoldo, Paul E. Kowalski, Monique Johnson, Javal Sheth, Alvaro Lassaletta, Ruth G. Tatevossian, Wilda Orisme, Ibrahim Qaddoumi, Lea F. Surrey, Marilyn M. Li, Angela J. Waanders, Stephen Gilheeney, Marc Rosenblum, Tejus Bale, Derek S. Tsang, Normand Laperriere, Abhaya Kulkarni, George M. Ibrahim, James Drake, Peter Dirks, Michael D. Taylor, James T. Rutka, Suzanne Laughlin, Manohar Shroff, Mary Shago, Lili-Naz Hazrati, Colleen DArcy, Vijay Ramaswamy, Ute Bartels, Annie Huang, Eric Bouffet, Matthias A. Karajannis, Mariarita Santi, David W. Ellison, Uri Tabori, Cynthia Hawkins

Issue&Volume: 2020/04/13

Abstract: Pediatric low-grade gliomas (pLGG) are frequently driven by genetic alterations inthe RAS-mitogen-activated protein kinase (RAS/MAPK) pathway yet show unexplained variabilityin their clinical outcome. To address this, we characterized a cohort of >1,000 clinicallyannotated pLGG. Eighty-four percent of cases harbored a driver alteration, while thosewithout an identified alteration also often exhibited upregulation of the RAS/MAPKpathway. pLGG could be broadly classified based on their alteration type. Rearrangement-driventumors were diagnosed at a younger age, enriched for WHO grade I histology, infrequentlyprogressed, and rarely resulted in death as compared with SNV-driven tumors. Furthersub-classification of clinical-molecular correlates stratified pLGG into risk categories.These data highlight the biological and clinical differences between pLGG subtypesand opens avenues for future treatment refinement.

DOI: 10.1016/j.ccell.2020.03.011

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(20)30151-3

期刊信息

Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：23.916
官方网址：https://www.cell.com/cancer-cell/home
投稿链接：https://www.editorialmanager.com/cancer-cell/default.aspx