Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma.
Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma.
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DOI：
10.1016/j.cell.2015.12.028
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发表时间：
2016-01-28
期刊：
影响因子：
64.5
通讯作者：
Verhaak RG
中科院分区：
文献类型：
--
作者：
Ceccarelli M;Barthel FP;Malta TM;Sabedot TS;Salama SR;Murray BA;Morozova O;Newton Y;Radenbaugh A;Pagnotta SM;Anjum S;Wang J;Manyam G;Zoppoli P;Ling S;Rao AA;Grifford M;Cherniack AD;Zhang H;Poisson L;Carlotti CG Jr;Tirapelli DP;Rao A;Mikkelsen T;Lau CC;Yung WK;Rabadan R;Huse J;Brat DJ;Lehman NL;Barnholtz-Sloan JS;Zheng S;Hess K;Rao G;Meyerson M;Beroukhim R;Cooper L;Akbani R;Wrensch M;Haussler D;Aldape KD;Laird PW;Gutmann DH;TCGA Research Network;Noushmehr H;Iavarone A;Verhaak RG
成人弥漫性胶质瘤的治疗开发受到对体细胞胶质瘤驱动改变和次优疾病分类的不完全了解的阻碍。我们从癌症基因组图谱中定义了与1，122个弥漫性II-III-IV级胶质瘤相关的完整基因集，并使用分子谱来改善疾病分类，确定分子相关性，并提供从低到高级别疾病进展的见解。全基因组测序数据分析确定ATRX而不是TERT启动子突变与端粒长度增加相关。通过分析DNA甲基化谱，总结了基于IDH突变和1 p/19 q共缺失状态的胶质瘤分类的最新进展，确定了临床相关的分子子集。IDH突变型胶质瘤的一个亚型与DNA去甲基化和预后差相关; IDH野生型弥漫性胶质瘤的一组显示与毛细胞星形细胞瘤的分子相似性和相对有利的生存。了解内聚性疾病组可能有助于改善临床结局。
Therapy development for adult diffuse glioma is hindered by incomplete knowledge of somatic glioma driving alterations and suboptimal disease classification. We defined the complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas from The Cancer Genome Atlas and used molecular profiles to improve disease classification, identify molecular correlations, and provide insights into the progression from low- to high-grade disease. Whole genome sequencing data analysis determined that ATRX but not TERT promoter mutations are associated with increased telomere length. Recent advances in glioma classification based on IDH mutation and 1p/19q co-deletion status were recapitulated through analysis of DNA methylation profiles, which identified clinically relevant molecular subsets. A subtype of IDH-mutant glioma was associated with DNA demethylation and poor outcome; a group of IDH-wildtype diffuse glioma showed molecular similarity to pilocytic astrocytoma and relatively favorable survival. Understanding of cohesive disease groups may aid improved clinical outcomes.