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Molecular Characterization of “True” Low-Grade IDH-Wildtype Astrocytomas
Journal of Neuropathology and Experimental Neurology ( IF 3.2 ) Pub Date : 2021-04-08 , DOI: 10.1093/jnen/nlab023
Timothy E Richardson 1 , Kimmo J Hatanpaa 2 , Jamie M Walker 1
Affiliation  

Numerous recent studies have demonstrated that the vast majority of IDH-wildtype astrocytomas with WHO grade II/III histology have clinical outcomes equivalent to IDH-wildtype glioblastomas. This has called into question the existence of an IDH-wildtype lower-grade astrocytoma (LGA) category, and the cIMPACT-NOW study group has suggested 3 molecular features which, if present, warrant upgrading IDH-wildtype LGA to glioblastoma: EGFR amplification, 7+/10−, and TERT promoter mutation. Herein, we evaluate the clinical, histologic, and molecular features of IDH-wildtype low-grade astrocytomas, defined here as infiltrative adult astrocytoma lacking histologic features of glioblastoma (microvascular proliferation and/or necrosis), IDH1/2 mutation, and all 3 of the cIMPACT-NOW update 3 factors. Compared with their counterparts with cIMPACT-NOW features of glioblastoma (LGA-C+; n = 108), IDH-wildtype LGAs lacking these features (LGA-C0; n = 36) occur in significantly younger patients, are more frequently WHO grade II, have less total copy number variation distributed across the entire genome, less frequent homozygous deletion of CDKN2A, less frequent PTEN and PIK3CA alterations, and more frequent NF1 alterations. These results suggest that although rare, a “true” IDH-wildtype LGA category does exist, and has distinct clinical and molecular features consistent with relatively beneficial clinical outcomes in these patients.

中文翻译:

“真正的”低级别 IDH-野生型星形细胞瘤的分子特征

最近的大量研究表明,绝大多数具有 WHO II/III 级组织学的 IDH 野生型星形细胞瘤具有与 IDH 野生型胶质母细胞瘤相当的临床结果。这对 IDH 野生型低级别星形细胞瘤 (LGA) 类别的存在提出了质疑,cIMPACT-NOW 研究组提出了 3 个分子特征,如果存在,则需要将 IDH 野生型 LGA 升级为胶质母细胞瘤:EGFR 扩增, 7+/10-,和 TERT 启动子突变。在此,我们评估了 IDH 野生型低级别星形细胞瘤的临床、组织学和分子特征,此处定义为浸润性成人星形细胞瘤,缺乏胶质母细胞瘤(微血管增殖和/或坏死)、IDH1/2 突变和所有 3 个组织学特征的浸润性成人星形细胞瘤。 cIMPACT-NOW 更新 3 个因素。与具有胶质母细胞瘤 cIMPACT-NOW 特征的对应物(LGA-C+;n = 108)相比,缺乏这些特征的 IDH-野生型 LGA(LGA-C0;n = 36)发生在显着年轻的患者中,更常见于 WHO II 级,在整个基因组中分布的总拷贝数变异较少,CDKN2A 纯合缺失的频率较低,PTEN 和 PIK3CA 改变的频率较低,而 NF1 的改变频率较高。这些结果表明,虽然罕见,但确实存在“真正的”IDH-野生型 LGA 类别,并且具有与这些患者相对有益的临床结果一致的独特临床和分子特征。在整个基因组中分布的总拷贝数变异较少,CDKN2A 纯合缺失的频率较低,PTEN 和 PIK3CA 改变的频率较低,而 NF1 的改变频率较高。这些结果表明,虽然罕见,但确实存在“真正的”IDH-野生型 LGA 类别,并且具有与这些患者相对有益的临床结果一致的独特临床和分子特征。在整个基因组中分布的总拷贝数变异较少,CDKN2A 纯合缺失的频率较低,PTEN 和 PIK3CA 改变的频率较低,而 NF1 的改变频率较高。这些结果表明,虽然罕见,但确实存在“真正的”IDH-野生型 LGA 类别,并且具有与这些患者相对有益的临床结果一致的独特临床和分子特征。
更新日期:2021-04-08
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