Fusion proteins in lung cancer: addressing diagnostic problems for deciding therapy

Expert Rev Anticancer Ther. 2021 Aug;21(8):887-900. doi: 10.1080/14737140.2021.1903875. Epub 2021 Mar 30.


Introduction: Gene fusions are frequent chromosomal aberrations in solid tumors. In Lung cancer (LC) several druggable-fusions involving tyrosine kinase receptor genes have been described, including ALK, ROS1, RET and NTRK. In non-small cell lung cancer, testing for targetable fusions has become a part of routine clinical practice, greatly impacting therapeutic choice for patients with these aberrations. Although substantial technologies for gene fusion detection have been implemented over time including; cytogenetic, Fluorescence in situ hybridization (FISH), Immunohistochemistry (IHC), Retro-transcription Real-Time PCR (RT-qPCR), to Next Generation Sequencing (NGS), nCounter system (Nanostring technology), several critical issues remain. To date, only the companion diagnostic tests FISH and IHC for ALK-rearrangements and NGS for ROS1-rearrangments were approved. Other fusion approved tests are currently unavailable.Areas covered: In this review, we explore current diagnostic problems of gene fusion detection relative to the technologies available, in order to clarify future standardization of analyses which determine therapeutic choices.Expert opinion: The establishment of a gold standard, an effective diagnostic algorithm, and a standardized interpretation for the analysis of each druggable-fusions in lung cancer is essential for adequate therapeutic management.

Keywords: ALK-rearrangements; NTRK-rearrangements; RET-rearrangements; ROS1-rearrangements; fluorescence in situ hybridization (FISH); immunohistochemistry (IHC); next generation sequencing (NGS); tyrosine kinase inhibitors.

Publication types

  • Review

MeSH terms

  • Anaplastic Lymphoma Kinase / genetics
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Gene Rearrangement
  • Humans
  • In Situ Hybridization, Fluorescence
  • Lung Neoplasms* / diagnosis
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / therapy
  • Oncogene Proteins, Fusion / genetics
  • Protein-Tyrosine Kinases / genetics
  • Proto-Oncogene Proteins / genetics


  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins
  • Anaplastic Lymphoma Kinase
  • Protein-Tyrosine Kinases