Purpose

We previously reported that there was a subgroup of IDH-mutated astrocytomas harboring only 19q-loss showing oligodendroglioma-like morphology and significantly longer overall survival (OS) compared with 19q-intact astrocytomas. The aim of this study was to further explore the biological characteristics of this possible subgroup and obtain insight into the mechanism of their relatively benign clinical behavior.

Methods

We compared gene expression pattern between five 19q-loss and five 19q-intact IDH-mutated astrocytomas by microarray analysis.

Results

By comparing expression levels of genes of 19q-loss astrocytomas to those of 19q-intact astrocytomas, 102 up-regulated genes and 162 down-regulated genes were extracted. The down-regulated genes clustered heavily to 19q and 4p while the up-regulated genes clustered to 4q. It was noteworthy that fibroblast growth factor 1 associated with stem cell maintenance and multiple genes associated with glioma progression were down-regulated in 19q-loss astrocytomas, and these results were validated with the independent TCGA data set. On t-SNE analysis of the 19q-loss astrocytomas with other IDH-mutant glioma subgroups from the TCGA datasets, the expression pattern of the 19q-loss astrocytomas showed no shift toward oligodendrogliomas with 1p/19q codeletion but rather constituted a subgroup of astrocytoma.

Conclusions

These findings suggested that 19q-loss in astrocytomas is more likely acquired event rather than an early event in oncogenesis like the 1p/19q-codeletion in oligodendrogliomas, and that the biological features of 19q-loss astrocytomas are possibly related to differentially expressed genes associated with stem cell maintenance and glioma progression.

中文翻译：

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19q缺失星形细胞瘤的基因表达谱表明与更好的预后相关的特定模式

目的

我们之前曾报道，与 19q 完整星形细胞瘤相比，有一个IDH突变星形细胞瘤亚组仅具有 19q 缺失，显示出少突胶质细胞瘤样形态和显着更长的总生存期 (OS)。本研究的目的是进一步探索该可能亚组的生物学特征，并深入了解其相对良性临床行为的机制。

方法

我们通过微阵列分析比较了五个 19q 缺失和五个 19q 完整IDH突变星形细胞瘤之间的基因表达模式。

结果

通过比较19q缺失星形细胞瘤与19q完整星形细胞瘤基因的表达水平，提取了102个上调基因和162个下调基因。下调基因集中在 19q 和 4p，而上调基因集中在 4q。值得注意的是，与干细胞维持相关的成纤维细胞生长因子 1 和与胶质瘤进展相关的多个基因在 19q 缺失型星形细胞瘤中被下调，这些结果通过独立的 TCGA 数据集得到验证。在对来自 TCGA 数据集的 19q 缺失型星形细胞瘤与其他IDH突变型胶质瘤亚组进行 t-SNE 分析时，19q 缺失型星形细胞瘤的表达模式显示没有向具有 1p/19q 共缺失的少突胶质细胞瘤转变，而是构成了星形细胞瘤的一个亚组。

结论

这些发现表明，星形细胞瘤中的 19q 缺失更可能是获得性事件，而不是肿瘤发生中的早期事件，如少突胶质细胞瘤中的 1p/19q 共缺失，并且 19q 缺失星形细胞瘤的生物学特征可能与与干细胞维持和胶质瘤进展。