Clinical stratification of glioblastoma based on alterations in retinoblastoma tumor suppressor protein (RB1) and association with the proneural subtype.
Clinical stratification of glioblastoma based on alterations in retinoblastoma tumor suppressor protein (RB1) and association with the proneural subtype.
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胶质母细胞瘤的临床分层基于视网膜细胞瘤抑制蛋白（RB1）的变化以及与胸部亚型的关联。
DOI：
10.1097/nen.0b013e31823fe8f1
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发表时间：
2012-01
影响因子：
3.2
通讯作者：
Phillips JJ
中科院分区：
文献类型：
--
作者：
Goldhoff P;Clarke J;Smirnov I;Berger MS;Prados MD;James CD;Perry A;Phillips JJ
最近的一项关于胶质母细胞瘤（GBM）异种移植物中CDK 4/6抑制剂的研究将视网膜母细胞瘤肿瘤抑制蛋白RB 1状态确定为肿瘤治疗效果的决定因素。由于需要进行临床适用的RB 1检测，我们评估了2种互补方法用于确定GBM中RB 1状态的实用性。使用荧光原位杂交（FISH）和免疫组织化学（IHC），我们分析了34个GBM，这些GBM也作为癌症基因组图谱（TCGA）的一部分进行了分子表征。通过IHC，4例肿瘤（11.8%）RB蛋白表达完全缺失，包括2例通过FISH检测RB 1纯合缺失，1例通过FISH检测RB 1半合子缺失并结合RB 1中的新型无义突变。与这些结果一致，在通过IHC检测的51个GBM的独立组中，我们证明了5个（9.8%）中的RB 1蛋白丢失。在TCGA数据的GBM分子亚型分析中，在170个肿瘤中的18个（10.6%）中观察到RB 1转录本表达的完全丧失，并且这些高度富集于但不限于前神经亚型（p < 0.01）。这些数据支持使用IHC确定临床GBM标本中的RB 1状态，并表明RB 1改变在某些GBM亚组中可能更常见。
A recent study of CDK4/6-inhibitors in glioblastoma (GBM) xenografts identified retinoblastoma tumor suppressor protein RB1 status as a determinant of tumor therapeutic efficacy. Because of the need for clinically applicable RB1 testing, we assessed the utility of 2 complementary methods for determining RB1 status in GBM. Using fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC), we analyzed 34 GBMs that had also undergone molecular characterization as part of The Cancer Genome Atlas (TCGA). By IHC, 4 tumors (11.8%) had complete loss of RB protein expression, including 2 with homozygous deletion of RB1 by FISH and 1 with hemizygous deletion of RB1 by FISH combined with a novel nonsense mutation in RB1. Consistent with these results, in an independent set of 51 GBMs tested by IHC we demonstrated loss of RB1 protein in 5 (9.8%). In GBM molecular subtype analysis of TCGA data, complete loss of RB1 transcript expression was seen in 18 of 170 tumors (10.6%) and these were highly enriched for, but not exclusive to, the proneural subtype (p < 0.01). These data support the use of IHC for determining RB1 status in clinical GBM specimens and suggest that RB1 alterations may be more common in certain GBM subgroups.