Catalog of 5' fusion partners in RET+ NSCLC Circa 2020

Sai-Hong Ignatius Ou1, Viola W Zhu1

  • 1Chao Family Comprehensive Cancer Center, Department of Medicine, Division of Hematology and Oncology, University of California Irvine School of Medicine, Orange, California.

Insights

Researchers identified 48 RET fusion partners in non-small cell lung cancer (NSCLC), including novel ones conferring resistance to EGFR inhibitors. Understanding these fusions is crucial for targeted therapy in RET-positive NSCLC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • RET fusions are actionable oncogenic drivers in non-small cell lung cancer (NSCLC).
  • Differential responses to therapies exist based on RET fusion partners (e.g., KIF5B-RET vs. non-KIF5B-RET).
  • Identifying fusion partners is critical for effective treatment strategies in RET-positive NSCLC.

Purpose of the Study:

  • To comprehensively identify and characterize fusion partners involving the RET gene in NSCLC.
  • To investigate novel RET fusion partners, particularly those associated with therapeutic resistance.

Main Methods:

  • Systematic review and analysis of published literature and congress proceedings.
  • Identification of unique RET fusion partners and intergenic rearrangements.

Main Results:

  • Identified 48 unique fusion partners for RET in NSCLC.
  • Discovered two novel fusion partners, CCNYL2 and TRIM24, in RET fusions.
  • These novel fusions were associated with resistance to EGFR tyrosine kinase inhibitors.

Conclusions:

  • The study expands the known landscape of RET fusions in NSCLC.
  • Novel RET fusion partners can confer resistance to existing targeted therapies.
  • Characterization of RET fusion partners is essential for developing next-generation therapies for NSCLC.

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