Li Zhaopei, Wang Hailong, Zhang Zhen, Meng Xiangwen, Liu Dujuan, Tang Yuanhua
Oncology Center, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Weiqi Road, Jinan, Shandong 250021, China.
First Dimension Biosciences (Suzhou) Co., Ltd., Building B8, Floor 5, BioBay, 218 Xinghu Street, Industrial Park District, Suzhou, Jiangsu 215126, China.
Genomics. 2021 Jul;113(4):1930-1939. doi: 10.1016/j.ygeno.2021.04.029. Epub 2021 Apr 18.
Gene mutation detection and the resulted precision-medicine therapy is transforming clinical practice. Here, we report the use of a custom-developed, medium-sized, pan-cancer probe panel for the detection of somatic and germline mutations. We used a hybridization capture-based NGS assay for targeted deep sequencing of all exons and selected introns of 181 key cancer driver genes, covering both inherited risks and somatic mutations. We performed paired-variant calling on tumor samples and their matched normal samples. We processed clinical patient samples of formalin-fixed, paraffin embedded tumors (FFPE samples) and cell-free peripheral blood (cfDNA samples). We found germline mutations of inherited cancer risk at 9%; and discovered a novel germline mutation in BRCA1. Somatic mutation rate in driver genes is at 73.1%, much higher than previously reported. On recommending precision-medicine therapeutics, we achieved 91.6% for patients with FFPE samples.
基因突变检测及由此产生的精准医疗疗法正在改变临床实践。在此，我们报告使用定制开发的中型泛癌探针组来检测体细胞和种系突变。我们采用基于杂交捕获的二代测序（NGS）检测方法，对181个关键癌症驱动基因的所有外显子和选定内含子进行靶向深度测序，涵盖遗传风险和体细胞突变。我们对肿瘤样本及其匹配的正常样本进行配对变异检测。我们处理了福尔马林固定、石蜡包埋肿瘤的临床患者样本（FFPE样本）和游离外周血样本（cfDNA样本）。我们发现9%的样本存在遗传性癌症风险的种系突变；并在BRCA1基因中发现了一种新的种系突变。驱动基因中的体细胞突变率为73.1%，远高于先前报道。在推荐精准医疗疗法方面，对于FFPE样本患者，我们的成功率达到了91.6%。
