Low Siew-Kee, Ariyasu Ryo, Uchibori Ken, Hayashi Rie, Chan Hiu Ting, Chin Yoon Ming, Akita Takahiro, Harutani Yuhei, Kiritani Ayu, Tsugitomi Ryosuke, Manabe Ryo, Ogusu Shinsuke, Amino Yoshiaki, Kitazono Satoru, Yanagitani Noriko, Nakamura Yusuke, Nishio Makoto
Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan.
Department of Thoracic Medical Oncology, the Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
Transl Lung Cancer Res. 2022 May;11(5):711-721. doi: 10.21037/tlcr-21-981.
Genomic profiling of tumors from cancer patients facilitates molecular-guided therapy. The turnaround time is one of important issues to deliver results timely for clinical decisions. The Ion Torrent™ Genexus™ Integrated Sequencer automates all next generation sequencing (NGS) workflows and delivers results within a day.
In this study, we conducted a feasibility study to evaluate the detection rate of genomic alterations from cell-free total nucleic acid (cfTNA, containing cfDNA and cfRNA) of 119 non-small cell lung cancer using Oncomine Precision Assay on Genexus™ Integrated Sequencer. Oncomine Precision Assay (OPA) covers actionable mutations, copy number variations and fusion genes and that are applicable for the selection of targeted therapy. cfTNA isolated from plasma (derived from 14 ml of blood) were subjected to the Genexus system for library construction, templating, sequencing, and data analyses.
The sequencing resulted in median overall depth of 35,773× and median molecular coverage of 2,192× with cfTNA input ranged from 11 to 36 ng. Among the 119 samples evaluated, we detected at least one genomic alteration in plasma cfTNA of 79 cases (66%). When comparing to standard-of-care testing, the sensitivity and specificity of mutation detection in non-small cell lung cancer related genes using liquid biopsy with Genexus-OPA ranged between 49-67% and 93-100%, respectively. 59% of actionable mutations, which were present in tumor tissues, were detected by the Genexus- Oncomine Precision Assay using plasma cfTNA. Among the 5 mutations detected from liquid biopsy only, three mutations are of level 1 evidence according to OncoKB database, highlighting the clinical utilities of liquid biopsy in addressing tumor heterogeneity. Extrathoracic metastasis and levels of lactate dehydrogenase (LDH), C-reactive protein (CRP) and Carcinoembryonic Antigen (CEA) are found to be associated with increased circulating tumor DNA detection.
The Genexus™ Integrated Sequencer system is an automated, accurate NGS system with short turnaround time (TAT) that could assist clinicians to make more timely decision.
癌症患者肿瘤的基因组分析有助于分子导向治疗。周转时间是及时为临床决策提供结果的重要问题之一。Ion Torrent™ Genexus™ 集成测序仪可自动完成所有下一代测序（NGS）工作流程，并在一天内给出结果。
在本研究中，我们进行了一项可行性研究，以评估使用Genexus™ 集成测序仪上的Oncomine Precision Assay对119例非小细胞肺癌患者的游离总核酸（cfTNA，包含cfDNA和cfRNA）进行基因组改变检测的比率。Oncomine Precision Assay（OPA）涵盖可指导治疗的突变、拷贝数变异和融合基因，适用于靶向治疗的选择。从血浆（来自14毫升血液）中分离出的cfTNA被用于Genexus系统进行文库构建、模板制备、测序和数据分析。
测序结果显示，cfTNA输入量在11至36纳克之间时，总体深度中位数为35773×，分子覆盖度中位数为2192×。在评估的119个样本中，我们在79例（66%）患者的血浆cfTNA中检测到至少一种基因组改变。与标准治疗检测相比，使用Genexus-OPA进行液体活检检测非小细胞肺癌相关基因突变的灵敏度和特异性分别在49%-67%和93%-100%之间。在肿瘤组织中存在的可指导治疗的突变中，59%可通过使用血浆cfTNA的Genexus-Oncomine Precision Assay检测到。在仅通过液体活检检测到的5个突变中，根据OncoKB数据库，有3个突变具有1级证据，突出了液体活检在解决肿瘤异质性方面的临床应用价值。发现胸外转移以及乳酸脱氢酶（LDH）、C反应蛋白（CRP）和癌胚抗原（CEA）水平与循环肿瘤DNA检测增加有关。
Genexus™ 集成测序仪系统是一种自动化、准确的NGS系统，周转时间短（TAT），可协助临床医生做出更及时的决策。
