【佳学基因检测】全外显子组测序揭示单个 NF1 丛状神经纤维瘤患者恶性转化和转移过程中的遗传变化顺序

基因检测多少钱一次1万八解剖

与专家交流肿瘤个性化药物研究路径发现《Clin Cancer Res》在. 2015 Sep 15;21(18):4201-11.发表了一篇题目为《全外显子组测序揭示单个 NF1 丛状神经纤维瘤患者恶性转化和转移过程中的遗传变化顺序》肿瘤靶向药物治疗基因检测临床研究文章。该研究由Angela C Hirbe , Sonika Dahiya , Christopher A Miller , Tiandao Li , Robert S Fulton , Xiaochun Zhang , Sandra McDonald , Katherine DeSchryver , Eric J Duncavage , Jessica Walrath , Karlyne M Reilly , Haley J Abel , Melike Pekmezci , Arie Perry , Timothy J Ley , David H Gutmann 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。

推广使用肿瘤基因检测的收入来源分析关键词：

全外显子组测序,NF1 丛, 恶性转化,转移

肿瘤靶向治疗基因检测临床应用结果

目的：恶性周围神经鞘瘤 (MPNST) 在 1 型神经纤维瘤病 (NF1) 患者中的发生频率增加，它们可能来自良性丛状神经纤维瘤前体。虽然之前的研究使用了多种发现方法来发现与 MPNST 发病机制相关的基因，但目前尚不清楚哪些分子事件与丛状神经纤维瘤的 MPNST 进化相关。实验设计：对代表丛状的活检材料进行全外显子组测序神经纤维瘤 (n = 3)、MPNST 和 14 年期间单个 NF1 个体的转移。其他验证案例用于评估参与恶性进展的候选基因，而小鼠 MPNST 模型用于功能分析。结果：随着肿瘤从良性发展为恶性，具有体细胞 NF1 基因突变的细胞比例增加，这表明MPNST 开发中的克隆过程。在原发性肿瘤和转移性病变中发现了拷贝数变异，包括 TP53 基因的一个拷贝丢失，但在良性前体病变中没有发现。发现了数量有限的具有非同义体细胞突变的基因（βIII-spectrin 和 ZNF208），其中一些在其他原发性和转移性 MPNST 样本中得到了验证。最后，在大多数 MPNST 中观察到增加的 βIII-Spectrin 表达，并且 shRNA 介导的敲低减少了小鼠体内 MPNST 的生长。结论：总的来说，跟踪单个 NF1 个体中 MPNST 分子进化的能力提供了新的见解对未来机制研究的疾病发病机制和进展很重要的遗传事件序列。

肿瘤发生与复发转移国际数据库描述：

Purpose: Malignant peripheral nerve sheath tumors (MPNST) occur at increased frequency in individuals with neurofibromatosis type 1 (NF1), where they likely arise from benign plexiform neurofibroma precursors. While previous studies have used a variety of discovery approaches to discover genes associated with MPNST pathogenesis, it is currently unclear what molecular events are associated with the evolution of MPNST from plexiform neurofibroma.Experimental design: Whole-exome sequencing was performed on biopsy materials representing plexiform neurofibroma (n = 3), MPNST, and metastasis from a single individual with NF1 over a 14-year period. Additional validation cases were used to assess candidate genes involved in malignant progression, while a murine MPNST model was used for functional analysis.Results: There was an increasing proportion of cells with a somatic NF1 gene mutation as the tumors progressed from benign to malignant, suggesting a clonal process in MPNST development. Copy number variations, including loss of one copy of the TP53 gene, were identified in the primary tumor and the metastatic lesion, but not in benign precursor lesions. A limited number of genes with nonsynonymous somatic mutations (βIII-spectrin and ZNF208) were discovered, several of which were validated in additional primary and metastatic MPNST samples. Finally, increased βIII-spectrin expression was observed in the majority of MPNSTs, and shRNA-mediated knockdown reduced murine MPNST growth in vivo.Conclusions: Collectively, the ability to track the molecular evolution of MPNST in a single individual with NF1 offers new insights into the sequence of genetic events important for disease pathogenesis and progression for future mechanistic study.