Targeted Next-generation-sequencing for Reliable Detection of Targetable Rearrangements in Lung Adenocarcinoma-a Single Center Retrospective Study

Overview

Journal Pathol Res Pract

Specialty Pathology

Date 2018 Mar 28

PMID 29580750

Citations 11

Authors

Nadezda P Velizheva

Markus P Rechsteiner

Nadejda Valtcheva

Sandra N Freiberger

Christine E Wong

Bart Vrugt

Qing Zhong

Ulrich Wagner

Holger Moch

Sven Hillinger

Isabelle Schmitt-Opitz

Alex Soltermann

Peter J Wild

Verena Tischler

Affiliations

Soon will be listed here.

Abstract

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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