【佳學(xué)基因檢測】新一代測序基因檢測在 1 型神經(jīng)纖維瘤病分子診斷中的應(yīng)用：一項驗證研究

靶向基因檢測2萬多重要性

挖掘腫瘤治療的前沿研究在《腫瘤致病基因檢測與轉(zhuǎn)移潛能分析》收錄《Genet Test Mol Biomarkers》在.?2014 Nov;18(11):722-35.發(fā)表了一篇題目為《新一代測序基因檢測在 1 型神經(jīng)纖維瘤病分子診斷中的應(yīng)用：一項驗證研究》腫瘤靶向藥物治療基因檢測臨床研究文章。該研究由Ryo Maruoka?,?Toshiki Takenouchi,?Chiharu Torii,?Atsushi Shimizu,?Kumiko Misu,?Koichiro Higasa,?Fumihiko Matsuda,?Arihito Ota,?Katsumi Tanito,?Akira Kuramochi,?Yoshimi Arima,?Fujio Otsuka,?Yuichi Yoshida,?Keiji Moriyama,?Michihito Niimura,?Hideyuki Saya,?Kenjiro Kosaki等完成。促進(jìn)了腫瘤的正確治療與個性化用藥的發(fā)展，進(jìn)一步強(qiáng)調(diào)了基因信息檢測與分析的重要性。

腫瘤藥物有效性臨床研究內(nèi)容關(guān)鍵詞：

新一代,下一代,基因檢測,基因測序,I型神經(jīng)纖維瘤,高通量測序,覆蓋率,

腫瘤靶向治療基因檢測臨床應(yīng)用結(jié)果

高通量測序基因檢測有效性評估的研究目的：腫瘤基因檢測項目組評估了下一代測序方案的有效性，該方案使用基于溶液內(nèi)雜交的富集來鑒定 NF1 突變，用于診斷 86 名原型遺傳綜合征（1 型神經(jīng)纖維瘤?。┗颊摺４送?，經(jīng)典遺傳的其他致病基因綜合征被設(shè)置為覆蓋分析的目標(biāo)基因。腫瘤基因檢測項目組研究結(jié)果：該協(xié)議確定了 30 個無意義突變、19 個移碼和 8 個剪接位點(diǎn)突變，以及 10 個先前被報道為致病的核苷酸替換。在其余 19 個樣本中，10 個具有通過多重連接依賴性探針擴(kuò)增方法檢測到的單外顯子或多外顯子缺失，3 個具有在正常 SNP 數(shù)據(jù)庫中未觀察到的錯義突變，并被預(yù)測為致病性。對同一診斷性基因檢測包中包含的 NF1 基因以外的基因進(jìn)行覆蓋率分析表明，平均覆蓋率為 115 倍，足以進(jìn)行突變檢測。高通量測序基因檢測有效性研究結(jié)論：使用目前報道的方法在 86 名符合排除10例大缺失患者時，臨床診斷標(biāo)準(zhǔn)為92.1%（70/76）。結(jié)果驗證了這種基于下一代測序的方法在診斷 1 型神經(jīng)纖維瘤病中的臨床實用性。根據(jù)覆蓋分析的結(jié)果，可以預(yù)期其他遺傳綜合征的檢測率相當(dāng)。

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

Aims:?We assessed the validity of a next-generation sequencing protocol using in-solution hybridization-based enrichment to identify NF1 mutations for the diagnosis of 86 patients with a prototypic genetic syndrome, neurofibromatosis type 1. In addition, other causative genes for classic genetic syndromes were set as the target genes for coverage analysis.Results:?The protocol identified 30 nonsense, 19 frameshift, and 8 splice-site mutations, together with 10 nucleotide substitutions that were previously reported to be pathogenic. In the remaining 19 samples, 10 had single-exon or multiple-exon deletions detected by a multiplex ligation-dependent probe amplification method and 3 had missense mutations that were not observed in the normal Japanese SNP database and were predicted to be pathogenic. Coverage analysis of the genes other than the NF1 gene included on the same diagnostic panel indicated that the mean coverage was 115-fold, a sufficient depth for mutation detection.Conclusions:?The overall mutation detection rate using the currently reported method in 86 patients who met the clinical diagnostic criteria was 92.1% (70/76) when 10 patients with large deletions were excluded. The results validate the clinical utility of this next-generation sequencing-based method for the diagnosis of neurofibromatosis type 1. Comparable detection rates can be expected for other genetic syndromes, based on the results of the coverage analysis.