【广东会GDH基因检测】新一代测序基因检测在 1 型神经纤维瘤病分子诊断中的应用：一项验证研究

靶向基因检测2万多重要性

挖掘肿瘤治疗的前沿研究在《肿瘤致病基因检测与转移潜能分析》收录《Genet Test Mol Biomarkers》在. 2014 Nov;18(11):722-35.发表了一篇题目为《新一代测序基因检测在 1 型神经纤维瘤病分子诊断中的应用：一项验证研究》肿瘤靶向药物治疗基因检测临床研究文章。该研究由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。促进了肿瘤的正确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。

肿瘤药物有效性临床研究内容关键词：

新一代,下一代,基因检测,基因测序,I型神经纤维瘤,高通量测序,覆盖率,

肿瘤靶向治疗基因检测临床应用结果

高通量测序基因检测有效性评估的研究目的：肿瘤基因检测项目组评估了下一代测序方案的有效性，该方案使用基于溶液内杂交的富集来鉴定 NF1 突变，用于诊断 86 名原型遗传综合征（1 型神经纤维瘤病）患者。此外，经典遗传的其他致病基因综合征被设置为覆盖分析的目标基因。肿瘤基因检测项目组研究结果：该协议确定了 30 个无意义突变、19 个移码和 8 个剪接位点突变，以及 10 个先前被报道为致病的核苷酸替换。在其余 19 个样本中，10 个具有通过多重连接依赖性探针扩增方法检测到的单外显子或多外显子缺失，3 个具有在正常 SNP 数据库中未观察到的错义突变，并被预测为致病性。对同一诊断性基因检测包中包含的 NF1 基因以外的基因进行覆盖率分析表明，平均覆盖率为 115 倍，足以进行突变检测。高通量测序基因检测有效性研究结论：使用目前报道的方法在 86 名符合排除10例大缺失患者时，临床诊断标准为92.1%（70/76）。结果验证了这种基于下一代测序的方法在诊断 1 型神经纤维瘤病中的临床实用性。根据覆盖分析的结果，可以预期其他遗传综合征的检测率相当。

肿瘤发生与反复转移国际数据库描述：

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.