Clonal variation in drug and radiation response among glioma-initiating cells is linked to proneural-mesenchymal transition (Methylation BeadChip)

Intra-tumor heterogeneity is a hallmark of glioblastoma multiforme, and thought to negatively affect treatment efficacy. Here we establish libraries of glioma-initiating cell (GIC) clones from patient samples and find extensive molecular and phenotypic variability between clones, including a wide range of responses to radiation and drugs. This widespread variability was observed as a continuum of multitherapy resistance phenotypes linked to a proneural-to-mesenchymal shift in the transcriptome. Affymetrix Illumina 450k array analyses were performed according to the manufacturer's directions on DNA extracted from 16 clonal malignant glioma cultures and 1 bulk cultures representing the parental material used to derive clones.

肿瘤内异质性（Intra-tumor heterogeneity）是多形性胶质母细胞瘤（glioblastoma multiforme）的标志性特征，且被认为会对治疗效果产生负面影响。本研究从患者样本中构建了胶质瘤起始细胞（glioma-initiating cell, GIC）克隆文库，发现克隆间存在广泛的分子与表型异质性，包括对放疗与药物治疗的多样化应答。这种广泛的异质性表现为多药耐药表型的连续谱系，其与转录组（transcriptome）中的前神经元-间充质转化相关。本研究按照生产商的操作指南，对提取自16株克隆性恶性胶质瘤培养物以及1株代表克隆起源亲本材料的批量培养物的DNA，开展了Affymetrix Illumina 450K芯片分析。