28P - Different genetic profiling in lung adenocarcinoma of smokers with and without chronic obstructive pulmonary disease (COPD): An exploratory analysi...

Date 15 April 2016
Event European Lung Cancer Conference 2016 (ELCC) 2016
Session Poster lunch
Topics Cancer in Special Situations
Thoracic Malignancies
Pathology/Molecular Biology
Basic Scientific Principles
Presenter Laura Bonanno
Citation Journal of Thoracic Oncology (2016) 11 (supplement 4): S57-S166. S1556-0864(16)X0004-4
Authors L. Bonanno1, M. Schiavon2, F. Lunardi2, M. Tebaldi3, D. Calistri3, G. Pasello1, P.F. Conte4, F. Rea2, S. Indraccolo5, F. Calabrese2
  • 1Medical Oncology 2, Istituto Oncologico Veneto IRCCS, 35128 - Padova/IT
  • 2Department Of Cardiothoracic And Vascular Sciences, Università degli Studi di Padova, 35128 - Padova/IT
  • 3Biosciences Laboratory, Istituto Tumori della Romagna I.R.S.T., Meldola/IT
  • 4Department Of Surgery, Oncology And Gastroenterology, Università degli Studi di Padova, 35128 - Padova/IT
  • 5Immunology And Molecular Oncology, Istituto Oncologico Veneto IRCCS, 35128 - Padova/IT

Abstract

Background

Smoke is the most recognized risk factor for both COPD and lung cancer. However, the risk of lung cancer is higher in smokers with COPD up to 6-fold with respect to non-COPD patients (pts) with comparable cigarette exposure. NGS is a sensitive method for analyzing several genes alterations simultaneously. We aimed to compare genetic profiling of lung adenocarcinomas from smokers with or without COPD.

Methods

We retrospectively collected twenty-eight surgical specimens of lung adenocarcinoma: 9 from COPD and 19 from non-COPD smoker pts. They were already genotyped for EGFR and KRAS mutations by Sanger Sequencing. All the samples were analyzed using a 30-gene NGS panel on MiSeq platform (Illumina). Five clinical samples of adenocarcinoma from non-smokers were also included in the study, as a control.

Results

NGS approach confirmed 100% of mutations detected by Sanger sequencing and identified 4 KRAS and 4 EGFR additional mutations. Half of them were in regions not covered by the routine molecular tests and their potential clinical impact is not defined. Using the cut-off values of >600 reads and >10% variant allele fraction, COPD pts showed a median value of 2 mutations, whereas non-COPD patients had a median of 1 mutation per sample. Interestingly, 2 NRAS mutations [L95H] were detected only in COPD patients, whereas MET [H148R, I560M, V237F] and NTRK2 [E142K, R136H, A13T] alterations were found only in smokers without COPD.

Conclusions

The exploratory analysis suggests potential usefulness of NGS analysis in disclosing molecular profiling of COPD lung adenocarcinomas. Even using a restricted lung cancer specific panel, different molecular profiling could be detected. The finding of specific molecular features in COPD pts has potential clinical application both in therapy and in prevention field. Confirmation of the data in a larger retrospective series and association with morphological features is ongoing.

Clinical trial identification

Legal entity responsible for the study

Istituto Oncologico Veneto

Funding

Istituto Oncologico Veneto

Disclosure

All authors have declared no conflicts of interest.