【佳學(xué)基因檢測】全外顯子組測序揭示單個 NF1 叢狀神經(jīng)纖維瘤患者惡性轉(zhuǎn)化和轉(zhuǎn)移過程中的遺傳變化順序

基因檢測多少錢一次1萬八解剖

與專家交流腫瘤個性化藥物研究路徑發(fā)現(xiàn)《Clin Cancer Res》在.?2015 Sep 15;21(18):4201-11.發(fā)表了一篇題目為《全外顯子組測序揭示單個 NF1 叢狀神經(jīng)纖維瘤患者惡性轉(zhuǎn)化和轉(zhuǎn)移過程中的遺傳變化順序》腫瘤靶向藥物治療基因檢測臨床研究文章。該研究由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。促進了腫瘤的正確治療與個性化用藥的發(fā)展，進一步強調(diào)了基因信息檢測與分析的重要性。

推廣使用腫瘤基因檢測的收入來源分析關(guān)鍵詞：

全外顯子組測序,NF1 叢, 惡性轉(zhuǎn)化,轉(zhuǎn)移

腫瘤靶向治療基因檢測臨床應(yīng)用結(jié)果

目的：惡性周圍神經(jīng)鞘瘤 (MPNST) 在 1 型神經(jīng)纖維瘤病 (NF1) 患者中的發(fā)生頻率增加，它們可能來自良性叢狀神經(jīng)纖維瘤前體。雖然之前的研究使用了多種發(fā)現(xiàn)方法來發(fā)現(xiàn)與 MPNST 發(fā)病機制相關(guān)的基因，但目前尚不清楚哪些分子事件與叢狀神經(jīng)纖維瘤的 MPNST 進化相關(guān)。實驗設(shè)計：對代表叢狀的活檢材料進行全外顯子組測序神經(jīng)纖維瘤 (n = 3)、MPNST 和 14 年期間單個 NF1 個體的轉(zhuǎn)移。其他驗證案例用于評估參與惡性進展的候選基因，而小鼠 MPNST 模型用于功能分析。結(jié)果：隨著腫瘤從良性發(fā)展為惡性，具有體細(xì)胞 NF1 基因突變的細(xì)胞比例增加，這表明MPNST 開發(fā)中的克隆過程。在原發(fā)性腫瘤和轉(zhuǎn)移性病變中發(fā)現(xiàn)了拷貝數(shù)變異，包括 TP53 基因的一個拷貝丟失，但在良性前體病變中沒有發(fā)現(xiàn)。發(fā)現(xiàn)了數(shù)量有限的具有非同義體細(xì)胞突變的基因（βIII-spectrin 和 ZNF208），其中一些在其他原發(fā)性和轉(zhuǎn)移性 MPNST 樣本中得到了驗證。賊后，在大多數(shù) MPNST 中觀察到增加的 βIII-Spectrin 表達，并且 shRNA 介導(dǎo)的敲低減少了小鼠體內(nèi) MPNST 的生長。結(jié)論：總的來說，跟蹤單個 NF1 個體中 MPNST 分子進化的能力提供了新的見解對未來機制研究的疾病發(fā)病機制和進展很重要的遺傳事件序列。

腫瘤發(fā)生與反復(fù)轉(zhuǎn)移國際數(shù)據(jù)庫描述：

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.