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The long tail of molecular alterations in non-small cell lung cancer: a single-institution experience of next-generation sequencing in clinical molecular diagnostics
  1. Caterina Fumagalli1,
  2. Davide Vacirca1,
  3. Alessandra Rappa1,
  4. Antonio Passaro2,
  5. Juliana Guarize3,
  6. Paola Rafaniello Raviele1,
  7. Filippo de Marinis2,
  8. Lorenzo Spaggiari3,4,
  9. Chiara Casadio1,
  10. Giuseppe Viale1,4,
  11. Massimo Barberis1,
  12. Elena Guerini-Rocco1,4
  1. 1 Division of Pathology and Laboratory Medicine, European Institute of Oncology, Milan, Italy
  2. 2 Division of Thoracic Oncology, European Institute of Oncology, Milan, Italy
  3. 3 Division of Thoracic Surgery, European Institute of Oncology, Milan, Italy
  4. 4 Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
  1. Correspondence to Dr Massimo Barberis, Division of Pathology and Laboratory Medicine, European Institute of Oncology, Milan 20141, Italy; massimo.barberis{at}


Background Molecular profiling of advanced non-small cell lung cancers (NSCLC) is essential to identify patients who may benefit from targeted treatments. In the last years, the number of potentially actionable molecular alterations has rapidly increased. Next-generation sequencing allows for the analysis of multiple genes simultaneously.

Aims To evaluate the feasibility and the throughput of next-generation sequencing in clinical molecular diagnostics of advanced NSCLC.

Methods A single-institution cohort of 535 non-squamous NSCLC was profiled using a next-generation sequencing panel targeting 22 actionable and cancer-related genes.

Results 441 non-squamous NSCLC (82.4%) harboured at least one gene alteration, including 340 cases (63.6%) with clinically relevant molecular aberrations. Mutations have been detected in all but one gene (FGFR1) of the panel. Recurrent alterations were observed in KRAS, TP53, EGFR, STK11 and MET genes, whereas the remaining genes were mutated in <5% of the cases. Concurrent mutations were detected in 183 tumours (34.2%), mostly impairing KRAS or EGFR in association with TP53 alterations.

Conclusions The study highlights the feasibility of targeted next-generation sequencing in clinical setting. The majority of NSCLC harboured mutations in clinically relevant genes, thus identifying patients who might benefit from different targeted therapies.

  • lung cancer
  • molecular pathology
  • cancer genetics

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  • Handling editor Runjan Chetty.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests EG-R and MB received consulting fees from ThermoFisher.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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