Novel Gene Fusions in Glioblastoma Tumor Tissue and Matched Patient Plasma

Wang, Lan; Yekula, Anudeep; Muralidharan, Koushik; Small, Julia L.; Rosh, Zachary S.; Kang, Keiko M.; Carter, Bob S.; Balaj, Leonora

doi:10.3390/cancers12051219

Open AccessArticle

Novel Gene Fusions in Glioblastoma Tumor Tissue and Matched Patient Plasma

by

Lan Wang

^1,†,

Anudeep Yekula

^1,†,

Koushik Muralidharan

¹,

Julia L. Small

¹

,

Zachary S. Rosh

¹,

Keiko M. Kang

^1,2,

Bob S. Carter

^1,* and

Leonora Balaj

^1,*

¹

Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02115, USA

²

School of Medicine, University of California San Diego, San Diego, CA 92092, USA

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally.

Cancers 2020, 12(5), 1219; https://doi.org/10.3390/cancers12051219

Submission received: 11 March 2020 / Revised: 27 April 2020 / Accepted: 7 May 2020 / Published: 13 May 2020

(This article belongs to the Special Issue Liquid Biopsy in Cancer)

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Abstract

Sequencing studies have provided novel insights into the heterogeneous molecular landscape of glioblastoma (GBM), unveiling a subset of patients with gene fusions. Tissue biopsy is highly invasive, limited by sampling frequency and incompletely representative of intra-tumor heterogeneity. Extracellular vesicle-based liquid biopsy provides a minimally invasive alternative to diagnose and monitor tumor-specific molecular aberrations in patient biofluids. Here, we used targeted RNA sequencing to screen GBM tissue and the matched plasma of patients (n = 9) for RNA fusion transcripts. We identified two novel fusion transcripts in GBM tissue and five novel fusions in the matched plasma of GBM patients. The fusion transcripts FGFR3-TACC3 and VTI1A-TCF7L2 were detected in both tissue and matched plasma. A longitudinal follow-up of a GBM patient with a FGFR3-TACC3 positive glioma revealed the potential of monitoring RNA fusions in plasma. In summary, we report a sensitive RNA-seq-based liquid biopsy strategy to detect RNA level fusion status in the plasma of GBM patients.

Keywords: glioblastoma; gene fusions; liquid biopsy; RNA-seq; extracellular vesicles

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MDPI and ACS Style

Wang, L.; Yekula, A.; Muralidharan, K.; Small, J.L.; Rosh, Z.S.; Kang, K.M.; Carter, B.S.; Balaj, L. Novel Gene Fusions in Glioblastoma Tumor Tissue and Matched Patient Plasma. Cancers 2020, 12, 1219. https://doi.org/10.3390/cancers12051219

AMA Style

Wang L, Yekula A, Muralidharan K, Small JL, Rosh ZS, Kang KM, Carter BS, Balaj L. Novel Gene Fusions in Glioblastoma Tumor Tissue and Matched Patient Plasma. Cancers. 2020; 12(5):1219. https://doi.org/10.3390/cancers12051219

Chicago/Turabian Style

Wang, Lan, Anudeep Yekula, Koushik Muralidharan, Julia L. Small, Zachary S. Rosh, Keiko M. Kang, Bob S. Carter, and Leonora Balaj. 2020. "Novel Gene Fusions in Glioblastoma Tumor Tissue and Matched Patient Plasma" Cancers 12, no. 5: 1219. https://doi.org/10.3390/cancers12051219

APA Style

Wang, L., Yekula, A., Muralidharan, K., Small, J. L., Rosh, Z. S., Kang, K. M., Carter, B. S., & Balaj, L. (2020). Novel Gene Fusions in Glioblastoma Tumor Tissue and Matched Patient Plasma. Cancers, 12(5), 1219. https://doi.org/10.3390/cancers12051219

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Novel Gene Fusions in Glioblastoma Tumor Tissue and Matched Patient Plasma

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