title: Clinicopathological Characteristics of RET Rearranged Lung Cancer in European Patients.
abstract: BACKGROUND
  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.
authors.affiliation: Center for Integrated Oncology Köln Bonn, Cologne, Germany; Lung Cancer Group Cologne, Department I for Internal Medicine, University Hospital of Cologne, Cologne, Germany; Network Genomic Medicine, Cologne, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Michels
authors.affiliation: Network Genomic Medicine, Cologne, Germany; Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Andreas Hans
authors.initials: AH
authors.lastname: Scheel
authors.affiliation: Center for Integrated Oncology Köln Bonn, Cologne, Germany; Lung Cancer Group Cologne, Department I for Internal Medicine, University Hospital of Cologne, Cologne, Germany; Network Genomic Medicine, Cologne, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Scheffler
authors.affiliation: Network Genomic Medicine, Cologne, Germany; Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Anne Maria
authors.initials: AM
authors.lastname: Schultheis
authors.affiliation: Department for Medical Oncology, Lucerne Cantonal Hospital, Lucerne, Switzerland.
authors.forename: Oliver
authors.initials: O
authors.lastname: Gautschi
authors.affiliation: Institute of Pathology, Lucerne Cantonal Hospital, Lucerne, Switzerland.
authors.forename: Franziska
authors.initials: F
authors.lastname: Aebersold
authors.affiliation: Institute of Pathology, Lucerne Cantonal Hospital, Lucerne, Switzerland.
authors.forename: Joachim
authors.initials: J
authors.lastname: Diebold
authors.affiliation: Department for Internal Medicine, Haematology and Oncology, University Hospital Innsbruck, Innsbruck, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Pall
authors.affiliation: Department for Oncology, University Hospital Basel, Basel, Switzerland.
authors.forename: Sacha
authors.initials: S
authors.lastname: Rothschild
authors.affiliation: Department for Cytopathology, University Hospital Basel, Basel, Switzerland.
authors.forename: Lukas
authors.initials: L
authors.lastname: Bubendorf
authors.affiliation: Gerhard-Domagk-Institute of Pathology, University Hospital of Münster, Münster, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hartmann
authors.affiliation: Network Genomic Medicine, Cologne, Germany; Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Lukas
authors.initials: L
authors.lastname: Heukamp
authors.affiliation: Institute of Pathology, University Hospital of Göttigen, Göttingen, Germany.
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Schildhaus
authors.affiliation: Network Genomic Medicine, Cologne, Germany; Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Fassunke
authors.affiliation: Network Genomic Medicine, Cologne, Germany; Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Michaela Angelika
authors.initials: MA
authors.lastname: Ihle
authors.affiliation: Network Genomic Medicine, Cologne, Germany; Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Helen
authors.initials: H
authors.lastname: Künstlinger
authors.affiliation: Network Genomic Medicine, Cologne, Germany; Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Carina
authors.initials: C
authors.lastname: Heydt
authors.affiliation: Center for Integrated Oncology Köln Bonn, Cologne, Germany; Lung Cancer Group Cologne, Department I for Internal Medicine, University Hospital of Cologne, Cologne, Germany; Network Genomic Medicine, Cologne, Germany.
authors.forename: Rieke
authors.initials: R
authors.lastname: Fischer
authors.affiliation: Center for Integrated Oncology Köln Bonn, Cologne, Germany; Lung Cancer Group Cologne, Department I for Internal Medicine, University Hospital of Cologne, Cologne, Germany; Network Genomic Medicine, Cologne, Germany.
authors.forename: Lucia
authors.initials: L
authors.lastname: Nogovà
authors.affiliation: Center for Integrated Oncology Köln Bonn, Cologne, Germany; Lung Cancer Group Cologne, Department I for Internal Medicine, University Hospital of Cologne, Cologne, Germany; Network Genomic Medicine, Cologne, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Mattonet
authors.affiliation: Institute of Medical Statistics, Informatics and Epidemiology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Hein
authors.affiliation: Institute of Medical Statistics, Informatics and Epidemiology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Adams
authors.affiliation: Thoracic Centre, Malteser Hospital Bonn/Rhein-Sieg, Bonn, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Gerigk
authors.affiliation: Departent for Pulmonology Cardiology and Allergology, Johanniter Hospital, Bonn, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schulte
authors.affiliation: Evangelic Lung Clinic Berlin, Department of Pneumology, Berlin, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Lüders
authors.affiliation: Evangelic Lung Clinic Berlin, Department of Pneumology, Berlin, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Grohé
authors.affiliation: Department for Hematology, Oncology and Gastroenterology, Maria Hilf Hospital Mönchengladbach, Mönchengladbach, Germany.
authors.forename: Ullrich
authors.initials: U
authors.lastname: Graeven
authors.affiliation: Private Practice for Oncology, Medical Centre II (Martinus Höfe), Olpe, Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Müller-Naendrup
authors.affiliation: Department for Internal Medicine, St. Vinzenz Hospital Cologne, Cologne, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Draube
authors.affiliation: Department for Pulmonology and Allergology, Bethanien Hospital Moers, Moers, Germany.
authors.forename: Karl-Otto
authors.initials: KO
authors.lastname: Kambartel
authors.affiliation: Department for Pulmonology/Allergology/Sleep Medicine and Respiratory Care, Florence-Nightingale-Hospital, Düsseldorf, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Krüger
authors.affiliation: Department for Pulmonology/Allergology/Sleep Medicine and Respiratory Care, Florence-Nightingale-Hospital, Düsseldorf, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Schulze-Olden
authors.affiliation: Department for Pulmonology and Thoracic Oncology, Lung Clinic Hemer, Hemer, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Serke
authors.affiliation: Lung Clinic Merheim, Hospitals of Cologne, Cologne, Germany.
authors.forename: Walburga
authors.initials: W
authors.lastname: Engel-Riedel
authors.affiliation: Clinic for Pulmonology and Allergology, Bethanien Hospital, Solingen, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Kaminsky
authors.affiliation: Clinic for Pulmonology and Allergology, Bethanien Hospital, Solingen, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: Randerath
authors.affiliation: Network Genomic Medicine, Cologne, Germany; Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Merkelbach-Bruse
authors.affiliation: Network Genomic Medicine, Cologne, Germany; Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Büttner
authors.affiliation: Center for Integrated Oncology Köln Bonn, Cologne, Germany; Lung Cancer Group Cologne, Department I for Internal Medicine, University Hospital of Cologne, Cologne, Germany; Network Genomic Medicine, Cologne, Germany. Electronic address: juergen.wolf@uk-koeln.de.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wolf
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D005060:Europe; D005260:Female; D005500:Follow-Up Studies; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011379:Prognosis; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D015514:Oncogene Proteins, Fusion; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human
keywords: Adenocarcinoma; Clinicopathological characteristics; NSCLC; RET rearrangement; Smoking history; TP53