Differences in molecular profiles of glioblastomas according to location.
Differences in molecular profiles of glioblastomas according to location.
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胶质母细胞瘤的分子谱因部位而异。
DOI：
10.1093/neuonc/noy172
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发表时间：
2019
期刊：
影响因子：
15.9
通讯作者：
Horbinski,Craig
中科院分区：
文献类型：
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作者：
Horbinski,Craig
大脑被概念化为一个独立的结构，但把它看作是几个连接在一起的器官可能更有帮助。皮质和白色物质、中线结构（基底神经节、丘脑和中脑）、脑干和小脑都以不同的速度成熟，并且每一个都有自己独特的细胞组成、神经化学和微环境。因此，某些类型的脑肿瘤在特定的发育阶段优先出现在特定的区域。随着人类从童年到青春期和成年期的发展，肿瘤的位置从幕下和中线转移到幕上和大脑半球。虽然毛细胞性星形细胞瘤和中线浸润性胶质瘤在儿童中更常见，但成年人更有可能发展为脑星形细胞瘤（包括胶质母细胞瘤或GBM）和少突胶质细胞瘤。1，2类似地，在脑肿瘤中观察到的遗传改变也存在空间和时间维度，即使在相同组织型的肿瘤中也是如此。BRAF融合最常见于儿童小脑毛细胞型星形细胞瘤，随着患者年龄增长和肿瘤位置转移到幕上而变得不那么常见。3组蛋白H3。3-在突变浸润性胶质瘤中，涉及K27的那些倾向于出现在非常年轻的患者的中线中，而G34的突变优先发生在青少年和年轻成人的半球肿瘤中。4异柠檬酸脱氢酶1（IDH 1）突变的弥漫性浸润性胶质瘤是20-40奥尔兹额叶和颞叶的特征，而胶质瘤由表皮生长因子受体（EGFR）驱动的可能性随着年龄的增长而增加。5在最新一期的《神经肿瘤学》中，Cho等人描述了一种相对常见的肿瘤GBM的分子特征，这种肿瘤发生在一个不常见的部位，小脑。尽管小脑约占大脑总重量的10%，但只有1%的GBM发生在那里，因此对这些肿瘤的详细分析非常罕见。作者分析了19例成人小脑GBM（C-GBM），显示了与幕上GBM（S-GBM）的一些有趣的相似之处和差异。尽管小脑肿瘤作为一个群体在儿童中比成人更常见，但C-GBM与S-GBM具有相同的中位患者年龄，并且两种实体在组织学上相似。与S-GBM不同，其中α地中海贫血/智力低下综合征X连锁（ATRX）的突变与IDH 1突变密切相关，EGFR改变很常见，作者发现C-GBM有时携带突变的ATRX而没有IDH 1突变，并且没有突变或扩增的EGFR。C-GBM还显示出更高频率的RAS和血小板衍生生长因子受体A（PDGFRA）的改变，以及细胞周期蛋白依赖性激酶4（CDK 4）和小鼠双微体2（MDM 2）的扩增。尽管C-GBM中IDH 1突变相对较少，但这些肿瘤不成比例地显示出mRNA表达的前神经模式。他们的C-GBM都不含任何组蛋白突变，尽管他们的队列在儿童和年轻成人患者中缺乏。端粒酶逆转录酶（TERT）启动子突变，这是高度特征性的S-GBM，目前只有2的19 C-GBM。其C-GBM的转录组和甲基化组模式更接近儿童和成人S-GBM，并且不类似于其他后颅窝肿瘤，如毛细胞性星形细胞瘤、室管膜瘤和髓母细胞瘤。即便如此，他们报告了存在“C-GBM肿瘤的幕下脑区域特异性甲基化模式”和在C-GBM中表达但不表达的特定基因。
The brain is conceptualized as a single discrete structure, but it may be more helpful to regard it as several organs wired together. The cortex and white matter, midline structures (basal ganglia, thalamus, and midbrain), brainstem, and cerebellum all mature at different rates, and each has its own distinct cellular composition, neurochemistry, and microenvironment. Thus, it follows that certain types of brain tumors preferentially arise in specific regions, at particular stages of development. As humans progress from childhood into adolescence and adulthood, tumor location shifts from the infratentorium and midline to the supratentorium and cerebral hemispheres. 1 While pilocytic astrocytomas and midline infiltrative gliomas are more common in children, adults are far more likely to develop cerebral astrocytomas (including glioblastomas, or GBM) and oligodendrogliomas. 1, 2 Similarly, there are spatial and temporal dimensions to the genetic alterations observed among brain tumors, even among tumors of the same histotype. BRAF fusions are most common in pediatric pilocytic astrocytomas arising in the cerebellum, and become less frequent as the patient ages and tumor location shifts to the supratentorium. 3 Among histone H3. 3-mutant infiltrative gliomas, those involving K27 tend to arise in the midline of very young patients, whereas mutations in G34 preferentially occur in hemispheric tumors in teenagers and young adults. 4 Diffusely infiltrative gliomas with mutations of isocitrate dehydrogenase 1 (IDH1) are characteristic of the frontal and temporal lobes in 20–40 year olds, while the likelihood of a glioma being driven by epidermal growth factor receptor (EGFR) increases with advanced age. 5 In the current issue of Neuro Oncology, Cho et al describe the molecular features of a relatively common tumor, GBM, arising in an uncommon location, the cerebellum. 6 Even though the cerebellum is approximately 10% of total brain weight, only 1% of GBMs occur there, making detailed analysis of these tumors rare. The authors analyzed 19 cerebellar GBMs (C-GBMs) from adult patients, showing some interesting similarities to and differences from supratentorial GBM (S-GBM).Although cerebellar tumors as a group are more common in children than adults, C-GBM had the same median patient age as S-GBM, and the 2 entities were similar histologically. Unlike S-GBM, in which mutations of alpha thalassemia/mental retardation syndrome X-linked (ATRX) are strongly associated with IDH1 mutations, and EGFR alterations are common, the authors found that C-GBMs sometimes carried mutant ATRX without IDH1 mutation, and did not have mutated or amplified EGFR. C-GBMs also showed a higher frequency of alterations of RAS and platelet derived growth factor receptor A (PDGFRA), and amplification of cyclin-dependent kinase 4 (CDK4) and murine double minute 2 (MDM2). Despite the relative paucity of IDH1 mutations in C-GBMs, these tumors disproportionately showed a proneural pattern of mRNA expression. None of their C-GBMs contained any histone mutations, although their cohort was lacking in children and younger adult patients. Telomerase reverse transcriptase (TERT) promoter mutations, which are highly characteristic of S-GBMs, were present in only 2 of 19 C-GBMs. The transcriptome and methylome patterns of their C-GBMs were closer to pediatric and adult S-GBMs, and did not resemble other posterior fossa tumors like pilocytic astrocytoma, ependymoma, and medulloblastoma. Even so, they reported the existence of “infratentorial brain regionspecific methylation patterns for C-GBM tumors” and specific genes expressed in C-GBM but not …