Targeted next-generation-sequencing for reliable detection of targetable rearrangements in lung adenocarcinoma—a single center retrospective study

  • Oncogenic rearrangements leading to targetable gene fusions are well-established cancer driver events in lung adenocarcinoma. Accurate and reliable detection of these gene fusions is crucial to select the appropriate targeted therapy for each patient. We compared the targeted next-generation-sequencing Oncomine Focus Assay (OFA; Thermo Fisher Scientific) with conventional ALK FISH and anti-Alk immunohistochemistry in a cohort of 52 lung adenocarcinomas (10 ALK rearranged, 18 non-ALK rearranged, and 24 untested cases). We found a sensitivity and specificity of 100% for detection of ALK rearrangements using the OFA panel. In addition, targeted next generation sequencing allowed us to analyze a set of 23 driver genes in a single assay. Besides EML4-ALK (11/52 cases), we detected EZR-ROS1 (1/52 cases), KIF5B-RET (1/52 cases) and MET-MET (4/52 cases) fusions. All EML4-ALK, EZR-ROS1 and KIF5B-RET fusions were confirmed by multiplexed targeted next generation sequencing assay (Oncomine Solid Tumor Fusion Transcript Kit, Thermo Fisher Scientific). All cases with EML4-ALK rearrangement were confirmed by Alk immunohistochemistry and all but one by ALK FISH. In our experience, targeted next-generation sequencing is a reliable and timesaving tool for multiplexed detection of targetable rearrangements. Therefore, targeted next-generation sequencing represents an efficient alternative to time-consuming single target assays currently used in molecular pathology.

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Author:Nadezda P. Velizheva, Markus Rechsteiner, Nadejda Valtcheva, Sandra N. Freiberger, Christine E. Wong, Bart Vrugt, Qing Zhong, Ulrich WagnerORCiD, Holger MochORCiDGND, Sven Hillinger, Isabelle Opitz, Alex Soltermann, Peter Johannes WildORCiDGND, Verena Tischler
Pubmed Id:
Parent Title (English):Pathology, research and practice
Place of publication:München
Document Type:Article
Year of Completion:2018
Date of first Publication:2018/02/16
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/10/18
Tag:ALK gene; Gene fusion; Lung adenocarcinoma; Next generation sequencing
Page Number:7
First Page:572
Last Page:578
© 2018 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY license (
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0