Concurrent TERT Amplifications in EGFR Mutated Lung Adenocarcinoma are Associated with Higher Levels of Copy Number Aberrations - A Hypothesis-Generating Study

Author(s): Su Ir Lyu, Steffen Hamm, Pierce Heiden, Michael Schultheis, Christina Ali-dousty, Sabine Merkelbach-Bruse, Reinhard Büttner, Philipp Lohneis, Anne Maria Schultheis

Objectives: EGFR mutated lung cancer is a molecular subtype of lung cancer that can be treated using EGFR targeting tyrosine kinase inhibitors. Despite improved survival rates of patients treated with these inhibitors, relapse and resistance remains a major concern. Concurrent mutations have recently been identified to drive disease outcome in EGFR mutated lung cancer. Here we sought to investigate the frequency and characteristics of TERT amplifications in EGFR L858R mutated lung cancer.

Materials and Methods: We performed a re-analysis of nine publicly available datasets concerning lung cancer.

Results: In this hypothesis generating study, we could show that tumors with TERT amplifications exhibited higher numbers of copy number alterations, indicating higher levels of genomic instability, potentially driving tumor biology in addition to EGFR mutations.

Conclusion: Taken together, our hypothesis-generating study indicates that the presence of TERT amplifications in EGFR mutated lung cancer represents a specific molecular subset of EGFR mutated carcinomas that need to be further analyzed to better understand their biology.