Targeted Next-Generation Sequencing in Molecular Subtyping of Lower-Grade Diffuse Gliomas Application of the World Health Organization's 2016 Revised Criteria for Central Nervous System Tumors
Targeted Next-Generation Sequencing in Molecular Subtyping of Lower-Grade Diffuse Gliomas Application of the World Health Organization's 2016 Revised Criteria for Central Nervous System Tumors
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DOI：
10.1016/j.jmoldx.2016.10.010
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发表时间：
2017-03-01
影响因子：
4.1
通讯作者：
Duncavage, Eric J.
中科院分区：
文献类型：
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作者：
Carter, Jamal H.;McNulty, Samantha N.;Duncavage, Eric J.
2007年世界卫生组织中枢神经系统肿瘤分类将低级别胶质瘤[LGGs(II级至III级弥漫性胶质瘤)]从形态上归类为星形细胞瘤或少突胶质细胞瘤，形态不清的肿瘤归类为少突胶质细胞瘤。世界卫生组织最新发布的(2016)分类纳入了分子数据。一个单一的定向下一代测序(NGS)小组被用来检测最初使用2007年标准分类的50例LGG病例的单核苷酸变异和拷贝数变异，其中包括36例寡星形细胞瘤、11例少突胶质细胞瘤、2例星形细胞瘤和1例LGG。将NGS结果与IHC分析和荧光原位杂交结果进行比较，以评估一致性并根据2016年的标准对肿瘤进行分类。所有病例的NGS结果与IHC分析结果一致。在3例患者中，NGS在区分节段性染色体缺失和全臂缺失方面优于荧光原位杂交。NGS法可将36例少突胶质细胞瘤重新分类为星形细胞瘤30例(IDH1/2突变型20例，IDH1/2野生型10例)，少突胶质细胞瘤6例，IDH1/2突变型星形细胞瘤1例。在这里，我们展示了一种单一的、有针对性的NGS检测可以作为根据世界卫生组织2016年诊断计划对LGG进行分类的唯一测试方式。与多模式方法相比，这种模式提供了更高的准确性和效率，同时减少了对标本组织的要求。
The 2007 World Health Organization Classification of Tumours of the Central Nervous System classifies lower-grade gliomas [LGGs (grades II to III diffuse gliomas)] morphologically as astrocytomas or oligodendrogliomas, and tumors with unclear ambiguous morphology as oligoastrocytomas. The World Health Organization's newly released (2016) classification incorporates molecular data. A single, targeted next-generation sequencing (NGS) panel was used for detecting single-nucleotide variation and copy number variation in 50 LGG cases originally classified using the 2007 criteria, including 36 oligoastrocytomas, 11 oligodendrogliomas, 2 astrocytomas, and 1 LGG not otherwise specified. NGS results were compared with those from IHC analysis and fluorescence in situ hybridization to assess concordance and to categorize the tumors according to the 2016 criteria. NGS results were concordant with those from IHC analysis in all cases. In 3 cases, NGS was superior to fluorescence in situ hybridization in distinguishing segmental chromosomal losses from whole-arm deletions. The NGS approach was effective in reclassifying 36 oligoastrocytomas as 30 astrocytomas (20 IDH1/2 mutant and 10 IDH1/2 wild type) and 6 oligodendrogliomas, and 1 otigodendroglioma as an astrocytoma (IDH1/2 mutant). Here we show that a single, targeted NGS assay can serve as the sole testing modality for categorizing LGG according to the World Health Organization's 2016 diagnostic scheme. This modality affords greater accuracy and efficiency while reducing specimen tissue requirements compared with multimodal approaches.