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Gene Fusions Detected in Plasma of Glioblastoma Patients, Suggesting New Approach to Liquid Biopsy

Key findings

  • Researchers at Massachusetts General Hospital used a sensitive RNA sequencing panel to screen for gene fusions in tumor tissue and plasma from nine patients with glioblastoma (three with known gene fusions, six without)
  • There was 100% concordance between common gene fusions detected by Mass General's Solid Fusion Assay and those detected by RNA sequencing in tumor tissue, indicating the specificity of the sequencing approach
  • Two novel fusion transcripts were identified in tumor tissue and five in plasma
  • The fusion transcripts FGFR3–TACC3 and VTI1A-TCF7L2 were detected in both tissue and matched plasma

Gene fusions—chromosomal alterations that result in a hybrid of two coding or regulatory sequences between genes—have been detected in 30% to 50% of patients with glioblastoma. In other tumor types, it's recently become clear that certain gene fusions help drive cancer growth and progression.

Expanding on previous research at Massachusetts General Hospital into the possibility of "liquid biopsy" for glioblastoma, published in Neuro-OncologyBob S. Carter, MD, PhD, chief of the Department of Neurosurgery at Mass General and neurosurgical oncologist at the Mass General Cancer CenterLeonora Balaj, PhD, investigator in Neurosurgery, Anudeep Yekula, MBBS, a neurosurgery research fellow, and colleagues have become the first to identify gene fusions in biofluid. They report the clinical implications of their work in Cancers.

Study Design

The study involved nine adults with glioblastoma—three with gene fusions and six without, according to the Mass General Solid Fusion Assay (Mass General assay). RNA was extracted from their tumor tissue and plasma and was sequenced and screened for 232 known fusion-related genes.

In plasma, the researchers studied RNA from extracellular vesicles (EVs). These lipid-protected nanoparticles are released by all cells, including cancer cells, and contain RNA reflecting the cell of origin. Those properties have inspired numerous studies that support the analysis of EVs from biofluids as an attractive noninvasive alternative to tumor tissue biopsy for diagnosis and monitoring of various cancers.

Tumor Tissue

Regarding the three patients who had gene fusions identified in tumor tissue by the Mass General assay:

  • Patient 1 had corresponding fusion transcripts identified by RNA sequencing
  • Patient 2 had a novel fusion transcript
  • Patient 3 had both a corresponding and a novel fusion transcript

There was a 100% concordance between the common gene fusions detected by the Mass General assay and RNA sequencing.


In plasma, RNA sequencing detected gene fusions in one of the three patients who had gene fusions reported by the Mass General assay and three of the six patients who did not. Five novel fusions were identified in plasma.

Hope for the Future

This is a proof-of-principle study, but several results already seem exciting. The fusion transcripts FGFR3-TACC3 and VTI1A-TCF7L2 were detected in both tissue and matched plasma, suggesting they might be useful as EV-based biomarkers.

Drugs targeting FGFR kinase activity have shown promise in clinical trials, and an assay is available that identifies all possible FGFR3–TACC3 variants in glioblastoma tissue. Moreover, FGFR3–TACC3 has been detected in other systemic cancers, including bladder, head and neck, lung, nasopharyngeal, esophageal squamous cell and cervical cancer. A liquid biopsy that could detect FGFR3–TACC3 would have far-reaching benefits.

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