1308P - RET translocation in adenocarcinoma of the lung

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Non-Small-Cell Lung Cancer, Metastatic
Translational Research
Presenter Sebastian Michels
Citation Annals of Oncology (2014) 25 (suppl_4): iv426-iv470. 10.1093/annonc/mdu349
Authors S. Michels1, A. Schultheis2, M. Scheffler1, T. Rosner1, S. Merkelbach-Bruse3, L.C. Heukamp3, W. Engel-Riedel4, M. Serke5, S. Krüger6, J. Benedikter7, U. Gerigk8, W. Schulte9, A. Draube10, Y. Ko11, R. Büttner3, J. Wolf1
  • 1Lung Cancer Group Cologne, University Hospital Cologne, 50937 - Cologne/DE
  • 2Institute Of Pathology, University Hospital Cologne, 50937 - Cologne/DE
  • 3Institute Of Pathology, University Hospital Cologne, Cologne/DE
  • 4Lunc Clinic Merheim, Hospital of Cologne, Cologne/DE
  • 5Thoracic Oncology, Hemer Lung Clinic, Hemer/DE
  • 6Department For Pneumology And Allergology, Florence-Nightingale Hospital, Düsseldorf/DE
  • 7Department For Pneumology And Pneumologic Oncology, Clinics Bogenhausen, Munich/DE
  • 8Department Of Thoracic Surgery, Malteser Hospital Bonn, Cologne/DE
  • 9Pneumology, Malteser Hospital, Bonn/DE
  • 10Department For Internal Medicine Iv, St. Vinzenz-Hospital, Cologne/DE
  • 11Department Of Oncology, Johanniter Hospital Bonn, Bonn/DE

Abstract

Aim

Rearrangements of RET have recently been described as rare driver mutations in adenocarcinomas of the lung. Only small cohorts of Asian patients bearing RET translocated adenocarcinoma have been described so far, resulting in uncertainty of the clinicopathologic characteristics of Caucasian patients.

Methods

In this study we have analysed tumor tissue of 700 patients by fluorescence in-situ hybridisation (Cyto Vision) for RET translocations and by next generation sequencing (Illumina MiSeq System) for mutations in a subset of 14 oncogenes. Clinical, pathological, and genetic characteristics of these patients are described and compared with a control group of non RET translocated patients .

Results

Among the total cohort of 700 patients we identified 12 patients with RET translocated adenocarcinoma, reflecting a prevalence of 1.7%. 7 patients had a translocation ratio of less than 0.4, whereas only 3 showed a translocation ratio of more than 0.6. The tumor of one patient showed high polysomy of the RET gene. RET translocation was co-occuring with TP53 mutations in 7 patients and with MET mutations (exon 14) in one patient. No further mutations and abberations, notably in EGFR, KRAS, ALK and ROS1 were found. Patients were first diagnosed at a median age of 51 years with a predominance for male patients (75%). Three patients were current and 4 former smokers at time of diagnosis.

Conclusions

Here we describe clinicopathological features in a cohort of RET translocation positive NSCLC. Rearrangements in the RET gene are mutually exclusive to known oncogenic abberations. Median age at diagnosis in this subgroup of patients was notably younger than in the RET translocation wild type cohort. In contrast to data published, our data suggests that RET translocations are not predominantly associated with female gender and never- or light-smoking history. This data points out the need for screening of young patients with oncogene mutation wild type adenocarcinoma and history of light or heavy smoking for RET rearrangement.

Disclosure

All authors have declared no conflicts of interest.