From the Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
J Neuropathol Exp Neurol. 2021 Dec 29;80(12):1092-1098. doi: 10.1093/jnen/nlab109.
A primitive neuronal component is a feature of some glioblastomas but defining molecular alterations of this histologic variant remains uncertain. We performed next-generation sequencing of 1500 tumor related genes on tissue from 9 patients with glioblastoma with a primitive component (G/PN) and analyzed 27 similar cases from the Cancer Genome Atlas (TCGA) dataset. Alterations in the RB pathway were identified in all of our patients' tumors and 81% of TCGA tumors with the retinoblastoma tumor suppressor gene (RB1) commonly affected. Although RB1 mutations were observed in some conventional glioblastomas, the allelic fractions of these mutations were significantly higher in tumors with a primitive neuronal component in both our and TCGA cohorts (median, 72% vs 25%, p < 0.001 and 80% vs 40%, p < 0.02, respectively). Further, in 78% of patients in our cohort, RB expression was lost by immunohistochemistry. Our findings indicate that alterations in the RB pathway are common in G/PNs and suggest that inactivation of RB1 may be a driving mechanism for the phenotype.
原始神经成分是某些胶质母细胞瘤的特征，但这种组织学变异的分子改变仍不确定。我们对 9 例具有原始成分（G/PN）的胶质母细胞瘤患者的组织进行了 1500 个肿瘤相关基因的下一代测序，并分析了癌症基因组图谱（TCGA）数据集的 27 个类似病例。我们所有患者的肿瘤中都发现了 RB 通路的改变，并且 RB1 视网膜母细胞瘤肿瘤抑制基因常见受影响，占 81%的 TCGA 肿瘤。虽然在一些常规胶质母细胞瘤中观察到 RB1 突变，但在我们和 TCGA 队列中具有原始神经元成分的肿瘤中，这些突变的等位基因分数明显更高（中位数，分别为 72%比 25%，p<0.001 和 80%比 40%，p<0.02）。此外，在我们队列中的 78%的患者中，免疫组化检测到 RB 表达缺失。我们的研究结果表明，RB 通路的改变在 G/PN 中很常见，并表明 RB1 的失活可能是该表型的驱动机制。
