【佳学基因检测】人类和鼠类 NF1 单倍体不足导致细胞周期和 DNA 修复途径扰动的证据

肿瘤基因检测龙头企业国产

在高峰论坛中博士医师年度双基练习体会到《BMC Genomics》在. 2010 Mar 22;11:194.发表了一篇题目为《人类和鼠类 NF1 单倍体不足导致细胞周期和 DNA 修复途径扰动的证据》肿瘤靶向药物治疗基因检测临床研究文章。该研究由Alexander Pemov, Caroline Park, Karlyne M Reilly, Douglas R Stewart等完成。促进了肿瘤的精准治疗与个性化用药的发展，进一步强调了基因信息检测与分析的重要性。

肿瘤靶向药物及精准治疗临床研究内容关键词：

肿瘤靶向治疗基因检测临床应用结果

基因解码基因检测的研究介绍：1 型神经纤维瘤病 (NF1) 是一种常见的单基因肿瘤易感性疾病，继发于肿瘤抑制基因 NF1 的突变。 NF1 的单倍体不足通过细胞间信号传导的变化促进了允许的致瘤环境，但是这种肿瘤促进作用的细胞内机制尚不清楚。大多数原代人类 NF1+/- 细胞难以获得，但已从大型 NF1 家族中收集了类淋巴母细胞系 (LCL)。基因解码基因检测假设 NF1 单倍体不足的遗传效应可以通过比较来自 NF1 受影响和未受影响的个体的体细胞、非肿瘤细胞 (LCL) 中的全基因组转录谱来辨别。作为异质性的跨物种过滤器，基因解码基因检测将两个人类亲属的基因解码基因检测的研究结果与来自年龄和性别匹配的 Nf1+/- 和野生型小鼠的脾源性 B 淋巴细胞的全基因组转录谱进行比较，并使用基因集富集分析 (GSEA)、Onto-Express、Pathway-Express 和 MetaCore 工具来识别在 NF1-单倍体不足中受干扰的基因。基因解码基因检测的研究结果：基因解码基因检测观察到人类 LCL 中 NF1 和 CD19+ 小鼠 B 淋巴细胞中 Nf1 的中度表达。使用 t 检验评估单个转录本，基因解码基因检测观察到 NF1-单倍体不足的 LCL 和 Nf1-单倍体不足的小鼠 B 淋巴细胞中转录组的适度表达差异。然而，GSEA、Onto-Express、Pathway-Express 和 MetaCore 分析确定了控制细胞周期、DNA 复制和修复、转录和翻译以及免疫反应的基因，这些基因在人类和小鼠的 NF1 单倍体不足条件下是最受干扰的。基因解码基因检测的研究结论：当基因的一个等位基因的缺失足以引起疾病时，就会出现单倍体不足。单倍体不足传统上被视为一种被动状态。基因解码基因检测对扰动的、上调的细胞周期和 DNA 修复途径的观察可能在功能上导致 NF1 单倍体不足作为一种“活跃状态”，最终促进野生型等位基因的丧失。

肿瘤发生与复发转移国际数据库描述：

Background: Neurofibromatosis type 1 (NF1) is a common monogenic tumor-predisposition disorder that arises secondary to mutations in the tumor suppressor gene NF1. Haploinsufficiency of NF1 fosters a permissive tumorigenic environment through changes in signalling between cells, however the intracellular mechanisms for this tumor-promoting effect are less clear. Most primary human NF1+/- cells are a challenge to obtain, however lymphoblastoid cell lines (LCLs) have been collected from large NF1 kindreds. We hypothesized that the genetic effects of NF1-haploinsufficiency may be discerned by comparison of genome-wide transcriptional profiling in somatic, non-tumor cells (LCLs) from NF1-affected and -unaffected individuals. As a cross-species filter for heterogeneity, we compared the results from two human kindreds to whole-genome transcriptional profiling in spleen-derived B lymphocytes from age- and gender-matched Nf1+/- and wild-type mice, and used gene set enrichment analysis (GSEA), Onto-Express, Pathway-Express and MetaCore tools to identify genes perturbed in NF1-haploinsufficiency.Results: We observed moderate expression of NF1 in human LCLs and of Nf1 in CD19+ mouse B lymphocytes. Using the t test to evaluate individual transcripts, we observed modest expression differences in the transcriptome in NF1-haploinsufficient LCLs and Nf1-haploinsuffiicient mouse B lymphocytes. However, GSEA, Onto-Express, Pathway-Express and MetaCore analyses identified genes that control cell cycle, DNA replication and repair, transcription and translation, and immune response as the most perturbed in NF1-haploinsufficient conditions in both human and mouse.Conclusions: Haploinsufficiency arises when loss of one allele of a gene is sufficient to give rise to disease. Haploinsufficiency has traditionally been viewed as a passive state. Our observations of perturbed, up-regulated cell cycle and DNA repair pathways may functionally contribute to NF1-haploinsufficiency as an "active state" that ultimately promotes the loss of the wild-type allele.

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