Combined RNA-NGS and DNA-NGS Maximizes Detection of Clinically Actionable Gene Fusions in Solid Tumors

Researchers from Tempus AI Inc., led by Bradley Bowles, have published a groundbreaking study on the use of combined RNA- and DNA-next-generation sequencing (NGS) to detect oncogenic gene fusions in solid tumors. The study, published in Cancer Research Communications, analyzed a large real-world cohort of 67,278 patients with various types of solid tumors, including non-small cell lung cancer, colorectal cancer, and breast cancer. The researchers found that concurrent RNA- and DNA-NGS increased the detection of driver gene fusions by 21% compared to DNA-NGS alone, and that gene fusions were observed in a range of cancers beyond their approved cancer indications.

Key Takeaways:

  • The study analyzed a large real-world cohort of 67,278 patients with various types of solid tumors.
  • Gene fusions were detected in 2.2% of patients (1497), with 21.1% (316) of patients having a fusion detected with matched-targeted therapy approved in all cancer indications.
  • Concurrent RNA- and DNA-NGS increased the detection of driver gene fusions by 21% compared to DNA-NGS alone.
  • Gene fusions were observed in a range of cancers beyond their approved cancer indications, with 29% (n=437) of detected fusions detected outside of an FDA-approved indication.
  • Emerging fusion drivers with targets in drug development were found in an additional 218 patients, with combined RNA- and DNA-NGS increasing detection of these variants by 127%.
  • The study supports the use of combined RNA-NGS and DNA-NGS to maximize detection of clinically actionable fusions with FDA-approved matched therapies.

Statistics:

  • 67,278 patients with various types of solid tumors were analyzed.
  • 1497 patients (2.2%) had at least one of nine fusions detected, each having an FDA-approved matched therapy in at least one indication.
  • 316 patients (21.1%) had a fusion detected (RET or NTRK1/2/3) with matched-targeted therapy approved in all cancer indications.
  • 29% (n=437) of detected fusions were detected outside of an FDA-approved indication.
  • Emerging fusion drivers with targets in drug development were found in 218 patients.
  • Combined RNA- and DNA-NGS increased detection of clinically actionable fusions by 21%.
  • Combined RNA- and DNA-NGS increased detection of emerging fusion drivers by 127%.

Sources:

  • Molecular characterization of oncogenic gene fusions in a large real-world cohort of solid tumors. Cancer Research Communications, 2025.
  • NewsRx. Studies in the Area of Solid Cancer Reported from Bradley Bowles and Co-Researchers (Molecular characterization of oncogenic gene fusions in a large real-world cohort of solid tumors). Drug Week. October 31, 2025; p 788.