Illumina HT-12 expression array data for Diffuse Intrinsic Pontine Glioma

Diffuse Intrinsic Pontine Glioma (DIPG) is a fatal brain cancer that arises in the brainstem of children with no effective treatment and near 100% fatality. The failure of most therapies can be attributed to the delicate location of these tumors and choosing therapies based on assumptions that DIPGs are molecularly similar to adult disease. Recent studies have unraveled the unique genetic make-up of this brain cancer with nearly 80% harboring a K27M-H3.3 or K27M-H3.1 mutation. However, DIPGs are still thought of as one disease with limited understanding of the genetic drivers of these tumors. To understand what drives DIPGs we integrated whole-genome-sequencing with methylation, expression and copy-number profiling, discovering that DIPGs are three molecularly distinct subgroups (H3-K27M, Silent, MYCN) and uncovering a novel recurrent activating mutation in the activin receptor ACVR1, in 20% of DIPGs. Mutations in ACVR1 were constitutively activating, leading to SMAD phosphorylation and increased expression of downstream activin signaling targets ID1 and ID2. Our results highlight distinct molecular subgroups and novel therapeutic targets for this incurable pediatric cancer. Illumina HT-12 arrays were performed according to the manufacturer's directions on RNA extracted from FFPE biopsy and autopsy brain tissue from DIPG patients. Gene expression profiling on Illumina HT-12 arrays was performed for 35 paediatric DIPG samples and 10 normal brain samples弥漫内生型桥脑胶质瘤（Diffuse Intrinsic Pontine Glioma, DIPG）是一种致命的儿童脑干部恶性肿瘤，目前暂无有效治疗方案，死亡率接近100%。多数治疗方案收效甚微，究其原因，一方面是这类肿瘤所处位置极其特殊，另一方面过往治疗策略的制定均基于“弥漫内生型桥脑胶质瘤在分子层面与成人脑肿瘤相似”的假设。近期研究揭示了该类脑癌独特的遗传特征：近80%的病例携带K27M-H3.3或K27M-H3.1突变。但目前学界仍将弥漫内生型桥脑胶质瘤视为单一疾病，对其肿瘤发生的遗传驱动因素的认知仍十分有限。为明确该疾病的驱动机制，研究团队将全基因组测序与甲基化分析、基因表达谱分析及拷贝数变异分析相结合，不仅发现弥漫内生型桥脑胶质瘤可分为三个分子亚型（H3-K27M型、沉默型、MYCN型），还在20%的病例中鉴定出激活素受体ACVR1的全新复发性激活突变。ACVR1突变可使受体组成型激活，进而引发SMAD蛋白磷酸化，并上调下游激活素信号通路靶基因ID1与ID2的表达水平。本研究成果为这款难治性儿童脑癌明确了独特的分子亚型与全新治疗靶点。研究人员按照试剂盒制造商的操作说明，使用Illumina HT-12芯片对取自弥漫内生型桥脑胶质瘤患者的福尔马林固定石蜡包埋（FFPE）活检及尸检脑组织样本中的RNA进行了检测。团队针对35例儿童弥漫内生型桥脑胶质瘤样本与10例正常脑组织样本，通过Illumina HT-12芯片完成了基因表达谱分析。