Correction to: Whole tumor analysis reveals early origin of the TERT promoter mutation and intercellular heterogeneity in TERT expression.
Correction to: Whole tumor analysis reveals early origin of the TERT promoter mutation and intercellular heterogeneity in TERT expression.
复制标题
更正：整个肿瘤分析揭示了 TERT 启动子突变的早期起源和 TERT 表达的细胞间异质性。
作者：
背景在大多数IDH野生型胶质母细胞瘤（GBM）和IDH突变型少突胶质细胞瘤（OD）中，TERT启动子突变（TPM）使肿瘤细胞永生化。以前的TPM克隆性研究显示了相互矛盾的结果。进行这项研究，以确定TPM是否是克隆的肿瘤范围scale.MethodsWe调查TPM克隆性的关系，在19 IDH-野生型GBM和10 IDH-突变OD使用3维全面的肿瘤采样推定的早期事件。我们对264个肿瘤样本进行了桑格测序，对187个肿瘤样本进行了深度扩增子测序。我们通过全外显子组测序获得肿瘤纯度和拷贝数估计值。TERT表达通过RNA-seq和RNAscope评估。TPM的变异等位基因频率（VAF）与GBM中10号染色体丢失（R= 0.85）、OD中IDH 1突变（R= 0.87）和肿瘤纯度（GBM R= 0.91; OD R= 0.90）正相关。 相比之下，癌基因扩增在MDM 4和大多数EGFR扩增的病例中是肿瘤范围的，但在MYCN和PDGFRA中是异质性的，并且在低纯度样本中显着高。TPM VAF是中度相关与TERT表达（R= 0.52 GBM;R= 0.65 OD）。TERT表达被检测到在一个子集的细胞，仅在TPM阳性样品，包括样品模棱两可的肿瘤。 然而，细胞间TERT表达的异质性表明肿瘤生长过程中的动态调节，TERT表达可能是肿瘤细胞特异性的生物标志物。
BackgroundTheTERTpromoter mutation (TPM) is acquired in mostIDH-wildtype glioblastomas (GBM) andIDH-mutant oligodendrogliomas (OD) enabling tumor cell immortality. Previous studies on TPM clonality show conflicting results. This study was performed to determine whether TPM is clonal on a tumor-wide scale.MethodsWe investigated TPM clonality in relation to presumed early events in 19IDH-wildtype GBM and 10IDH-mutant OD using 3-dimensional comprehensive tumor sampling. We performed Sanger sequencing on 264 tumor samples and deep amplicon sequencing on 187 tumor samples. We obtained tumor purity and copy number estimates from whole exome sequencing.TERTexpression was assessed by RNA-seq and RNAscope.ResultsWe detected TPM in 100% of tumor samples with quantifiable tumor purity (219 samples). Variant allele frequencies (VAF) of TPM correlate positively with chromosome 10 loss in GBM (R= 0.85),IDH1mutation in OD (R= 0.87), and with tumor purity (R= 0.91 for GBM;R= 0.90 for OD). In comparison, oncogene amplification was tumor-wide forMDM4- and mostEGFR-amplified cases but heterogeneous forMYCNandPDGFRA, and strikingly high in low-purity samples. TPM VAF was moderately correlated withTERTexpression (R= 0.52 for GBM;R= 0.65 for OD).TERTexpression was detected in a subset of cells, solely in TPM-positive samples, including samples equivocal for tumor.ConclusionsOn a tumor-wide scale, TPM is among the earliest events in glioma evolution. Intercellular heterogeneity ofTERTexpression, however, suggests dynamic regulation during tumor growth.TERTexpression may be a tumor cell-specific biomarker.