Clinicopathological Characteristics of RET Rearranged Lung Cancer in European Patients

Sebastian Michels, Andreas Hans Scheel, Matthias Scheffler, Anne Maria Schultheis, Oliver Gautschi, Franziska Aebersold, Joachim Diebold, Georg Pall, Sacha Rothschild, Lukas Bubendorf, Wolfgang Hartmann, Lukas Heukamp, Hans-Ulrich Schildhaus, Jana Fassunke, Michaela Angelika Ihle, Helen Künstlinger, Carina Heydt, Rieke Fischer, Lucia Nogovà, Christian Mattonet, Rebecca Hein, Anne Adams, Ulrich Gerigk, Wolfgang Schulte, Heike Lüders, Christian Grohé, Ullrich Graeven, Clemens Müller-Naendrup, Andreas Draube, Karl-Otto Kambartel, Stefan Krüger, Susanne Schulze-Olden, Monika Serke, Walburga Engel-Riedel, Britta Kaminsky, Winfried Randerath, Sabine Merkelbach-Bruse, Reinhard Büttner, Jürgen Wolf, Sebastian Michels, Andreas Hans Scheel, Matthias Scheffler, Anne Maria Schultheis, Oliver Gautschi, Franziska Aebersold, Joachim Diebold, Georg Pall, Sacha Rothschild, Lukas Bubendorf, Wolfgang Hartmann, Lukas Heukamp, Hans-Ulrich Schildhaus, Jana Fassunke, Michaela Angelika Ihle, Helen Künstlinger, Carina Heydt, Rieke Fischer, Lucia Nogovà, Christian Mattonet, Rebecca Hein, Anne Adams, Ulrich Gerigk, Wolfgang Schulte, Heike Lüders, Christian Grohé, Ullrich Graeven, Clemens Müller-Naendrup, Andreas Draube, Karl-Otto Kambartel, Stefan Krüger, Susanne Schulze-Olden, Monika Serke, Walburga Engel-Riedel, Britta Kaminsky, Winfried Randerath, Sabine Merkelbach-Bruse, Reinhard Büttner, Jürgen Wolf

Abstract

Introduction: Rearrangements of RET are rare oncogenic events in patients with non-small cell lung cancer (NSCLC). While the characterization of Asian patients suggests a predominance of nonsmokers of young age in this genetically defined lung cancer subgroup, little is known about the characteristics of non-Asian patients. We present the results of an analysis of a European cohort of patients with RET rearranged NSCLC.

Methods: Nine hundred ninety-seven patients with KRAS/EGFR/ALK wildtype lung adenocarcinomas were analyzed using fluorescence in situ hybridization for RET fusions. Tumor specimens were molecularly profiled and clinicopathological characteristics of the patients were collected.

Results: Rearrangements of RET were identified in 22 patients, with a prevalence of 2.2% in the KRAS/EGFR/ALK wildtype subgroup. Co-occurring genetic aberrations were detected in 10 patients, and the majority had mutations in TP53. The median age at diagnosis was 62 years (range, 39-80 years; mean ± SD, 61 ± 11.7 years) with a higher proportion of men (59% versus 41%). There was only a slight predominance of nonsmokers (54.5%) compared to current or former smokers (45.5%).

Conclusions: Patients with RET rearranged adenocarcinomas represent a rare and heterogeneous NSCLC subgroup. In some contrast to published data, we see a high prevalence of current and former smokers in our white RET cohort. The significance of co-occurring aberrations, so far, is unclear.

Keywords: Adenocarcinoma; Clinicopathological characteristics; NSCLC; RET rearrangement; Smoking history; TP53.

Copyright © 2015 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Source: PubMed

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