RNA sequencing effectively identifies gene fusions undetected by DNA sequencing in lung adenocarcinomas

Background: Next-generation sequencing of DNA, which can provide valid information for clinical therapeutic decision-making, has been widely used in the management of lung cancer especially adenocarcinoma. However, due to its technical limitations for detecting certain alterations such as gene rearrangement, the DNA-based sequencing (DNA-seq) may miss the actionable alteration in some cases, who would have benefited from targeted therapy. The study aimed to evaluate the capability of RNA sequencing (RNA-seq) in identifying DNA-seq undetectable gene alterations in lung adenocarcinomas. Conclusions: Targeted RNA-seq can effectively identify genomic rearrangements that are undetectable by DNA-seq and provide lung adenocarcinoma patients with more opportunities for targeted therapy. Therefore, it should be recommended for all patients, in whom DNA-seq fails to detect driver alteration. READ ARTICLE

Journal of Clinical Oncology DOI:10.1200/JCO.2021.39.15_suppl.3052

Authors: Ruiying Zhao, Yuchen Han, Chan Xiang, Shengnan Chen, Jikai Zhao, Lianying Guo, Anbo Yu, Jinchen Shao, Lei Zhu, Yue Tian, Fan Yang, Lin Shao, Xuejing Li, Lu Zhang

Conference PaperKirk SmithMay 28, 2021RNA sequencing, DNA sequencing, lung adenocarcinoma

Potential Unreliability of Uncommon ALK, ROS1, and RET Genomic Breakpoints in Predicting the Efficacy of Targeted Therapy in NSCLC

Introduction: Variable genomic breakpoints have been identified through the application of target-capture DNA next-generation sequencing (NGS) for ALK, ROS1, and RET fusion detection in NSCLC. We investigated whether ALK, ROS1, and RET genomic breakpoint location can predict matched targeted therapy efficacy. Conclusions: Uncommon ALK, ROS1, and RET genomic breakpoint is an unreliable predictor of matched targeted therapy efficacy. Functional validation by RNA or protein assay may add value for the accurate detection and interpretation of rare fusions. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2020.10.156

Authors: Weihua Li, Lei Guo, Yutao Liu, Lin Dong, Lin Yang, Li Chen, Kaihua Liu, Yang Shao, Jianming Ying

Optimizing Mutation and Fusion Detection in NSCLC by Sequential DNA and RNA Sequencing

Introduction: Frequently, patients with locally advanced or metastatic NSCLC are screened for mutations and fusions. In most laboratories, molecular workup includes a multitude of tests: immunohistochemistry (ALK, ROS1, and programmed death-ligand 1 testing), DNA sequencing, in situ hybridization for fusion, and amplification detection. With the fast-emerging new drugs targeting specific fusions and exon-skipping events, this procedure harbors a growing risk of tissue exhaustion... Conclusions: We conclude that sequentially combining DNA NGS and RNA NGS is the most efficient strategy for mutation and fusion detection in smoking-associated NSCLC, whereas for never smokers we recommend a parallel approach. This approach was shown to be feasible on small tissue samples including for cytology tests, can drastically reduce the complexity and cost of molecular workup, and also provides flexibility in the constantly evolving landscape of actionable targets in NSCLC. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2020.01.019

Authors: Danielle Cohen, Liesbeth M. Hondelink, Nienke Solleveld-Westerink, Sandra M. Uljee, Dina Ruano, Anne-Marie Cleton-Jansen, Jan H. von der Thüsen, S. Rajen S. Ramai, Pieter E. Postmus, Jacob F. Graadt van Roggen, Bart P. C. Hoppe, Pieter C. Clahsen, Klaartje W. Maas, Els J. M. Ahsmann, Alexandraten Heuvel, Frank Smedts, Ronald N. van Rossem,Tomvan Wezel