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Transcriptional analyses of adult and pediatric adamantinomatous craniopharyngioma reveals similar expression signatures regarding potential therapeutic targets.
Acta Neuropathologica Communications ( IF 6.2 ) Pub Date : 2020-05-13 , DOI: 10.1186/s40478-020-00939-0
Eric Prince 1, 2 , Ros Whelan 3 , Andrew Donson 2, 4 , Susan Staulcup 1 , Astrid Hengartner 1, 2 , Trinka Vijmasi 1, 2 , Chibueze Agwu 5 , Kevin O Lillehei 3 , Nicholas K Foreman 2, 4 , James M Johnston 6 , Luca Massimi 7, 8 , Richard C E Anderson 9 , Mark M Souweidane 10, 11 , Robert P Naftel 12 , David D Limbrick 13, 14 , Gerald Grant 15 , Toba N Niazi 16 , Roy Dudley 17 , Lindsay Kilburn 18, 19 , Eric M Jackson 20 , George I Jallo 21 , Kevin Ginn 22 , Amy Smith 23 , Joshua J Chern 24, 25 , Amy Lee 26, 27 , Annie Drapeau 28 , Mark D Krieger 29 , Michael H Handler 1 , Todd C Hankinson 1, 2 ,
Affiliation  

Adamantinomatous craniopharyngioma (ACP) is a biologically benign but clinically aggressive lesion that has a significant impact on quality of life. The incidence of the disease has a bimodal distribution, with peaks occurring in children and older adults. Our group previously published the results of a transcriptome analysis of pediatric ACPs that identified several genes that were consistently overexpressed relative to other pediatric brain tumors and normal tissue. We now present the results of a transcriptome analysis comparing pediatric to adult ACP to identify biological differences between these groups that may provide novel therapeutic insights or support the assertion that potential therapies identified through the study of pediatric ACP may also have a role in adult ACP. Using our compiled transcriptome dataset of 27 pediatric and 9 adult ACPs, obtained through the Advancing Treatment for Pediatric Craniopharyngioma Consortium, we interrogated potential age-related transcriptional differences using several rigorous mathematical analyses. These included: canonical differential expression analysis; divisive, agglomerative, and probabilistic based hierarchical clustering; information theory based characterizations; and the deep learning approach, HD Spot. Our work indicates that there is no therapeutically relevant difference in ACP gene expression based on age. As such, potential therapeutic targets identified in pediatric ACP are also likely to have relvance for adult patients.

中文翻译:

对成人和小儿金刚起瘤性颅咽管瘤的转录分析显示出关于潜在治疗靶点的相似表达特征。

精金型颅咽管瘤(ACP)是一种生物学上良性但临床上具有侵略性的病变,对生活质量产生重大影响。该病的发病率呈双峰分布,在儿童和老年人中出现高峰。我们小组先前发表了儿科ACP转录组分析的结果,该研究确定了相对于其他儿科脑肿瘤和正常组织而言始终过量表达的几个基因。我们现在介绍将儿科和成人ACP进行比较的转录组分析结果,以鉴定这些人群之间的生物学差异,这可能会提供新颖的治疗见解,或支持通过儿科ACP研究确定的潜在疗法也可能在成人ACP中起作用的主张。使用我们通过小儿颅咽管瘤联合会的先进治疗获得的27个儿科和9个成人ACP的转录组数据集,我们使用了一些严格的数学分析方法来查询与年龄相关的潜在转录差异。其中包括:典型差异表达分析;基于分裂,聚集和概率的层次聚类;基于信息论的表征;以及深度学习方法HD Spot。我们的工作表明,基于年龄的ACP基因表达没有治疗上的相关差异。这样,在小儿ACP中确定的潜在治疗靶标也可能对成年患者具有吸引力。我们使用几种严格的数学分析方法来询问与年龄相关的潜在转录差异。其中包括:典型差异表达分析;基于分裂,聚集和概率的层次聚类;基于信息论的表征;以及深度学习方法HD Spot。我们的工作表明,基于年龄的ACP基因表达没有治疗上的相关差异。因此,在儿科ACP中确定的潜在治疗靶标也可能对成年患者有所帮助。我们使用几种严格的数学分析方法来询问与年龄相关的潜在转录差异。其中包括:典型差异表达分析;基于分裂,聚集和概率的层次聚类;基于信息论的表征;以及深度学习方法HD Spot。我们的工作表明,基于年龄的ACP基因表达没有治疗上的相关差异。这样,在小儿ACP中确定的潜在治疗靶标也可能对成年患者具有吸引力。我们的工作表明,基于年龄的ACP基因表达没有治疗上的相关差异。这样,在小儿ACP中确定的潜在治疗靶标也可能对成年患者具有吸引力。我们的工作表明,基于年龄的ACP基因表达没有治疗上的相关差异。这样,在小儿ACP中确定的潜在治疗靶标也可能对成年患者具有吸引力。
更新日期:2020-05-13
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