Carter Jamal H, McNulty Samantha N, Cimino Patrick J, Cottrell Catherine E, Heusel Jonathan W, Vigh-Conrad Katinka A, Duncavage Eric J
Department of Pathology and Immunology, Washington University, St. Louis, Missouri.
Department of Pathology, Division of Neuropathology, University of Washington, Seattle, Washington.
J Mol Diagn. 2017 Mar;19(2):328-337. doi: 10.1016/j.jmoldx.2016.10.010. Epub 2016 Dec 30.
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 oligodendroglioma 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.
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至III级弥漫性胶质瘤）]在形态学上分类为星形细胞瘤或少突胶质细胞瘤，形态不明确的肿瘤分类为少突星形细胞瘤。世界卫生组织新发布的（2016年）分类纳入了分子数据。使用单一的靶向二代测序（NGS）检测板，对最初根据2007年标准分类的50例LGG病例进行单核苷酸变异和拷贝数变异检测，其中包括36例少突星形细胞瘤、11例少突胶质细胞瘤、2例星形细胞瘤和1例未另行指定的LGG。将NGS结果与免疫组化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年标准对肿瘤进行分类。所有病例的NGS结果与免疫组化分析结果一致。在3例病例中，NGS在区分节段性染色体缺失和整条染色体臂缺失方面优于荧光原位杂交。NGS方法有效地将36例少突星形细胞瘤重新分类为30例星形细胞瘤（20例IDH1/2突变型和10例IDH1/2野生型）和6例少突胶质细胞瘤，以及将1例少突胶质细胞瘤重新分类为星形细胞瘤（IDH1/2突变型）。在此我们表明，单一的靶向NGS检测可作为根据世界卫生组织2016年诊断方案对LGG进行分类的唯一检测方式。与多模式方法相比，这种方式具有更高的准确性和效率，同时减少了对标本组织的需求。
