Cargando…

Novel Gene Fusions in Glioblastoma Tumor Tissue and Matched Patient Plasma

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. Extracellu...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Lan, Yekula, Anudeep, Muralidharan, Koushik, Small, Julia L., Rosh, Zachary S., Kang, Keiko M., Carter, Bob S., Balaj, Leonora
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281415/
https://www.ncbi.nlm.nih.gov/pubmed/32414213
http://dx.doi.org/10.3390/cancers12051219
_version_ 1783543914611867648
author Wang, Lan
Yekula, Anudeep
Muralidharan, Koushik
Small, Julia L.
Rosh, Zachary S.
Kang, Keiko M.
Carter, Bob S.
Balaj, Leonora
author_facet Wang, Lan
Yekula, Anudeep
Muralidharan, Koushik
Small, Julia L.
Rosh, Zachary S.
Kang, Keiko M.
Carter, Bob S.
Balaj, Leonora
author_sort Wang, Lan
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7281415
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-72814152020-06-19 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 Cancers (Basel) Article 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. MDPI 2020-05-13 /pmc/articles/PMC7281415/ /pubmed/32414213 http://dx.doi.org/10.3390/cancers12051219 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Lan
Yekula, Anudeep
Muralidharan, Koushik
Small, Julia L.
Rosh, Zachary S.
Kang, Keiko M.
Carter, Bob S.
Balaj, Leonora
Novel Gene Fusions in Glioblastoma Tumor Tissue and Matched Patient Plasma
title Novel Gene Fusions in Glioblastoma Tumor Tissue and Matched Patient Plasma
title_full Novel Gene Fusions in Glioblastoma Tumor Tissue and Matched Patient Plasma
title_fullStr Novel Gene Fusions in Glioblastoma Tumor Tissue and Matched Patient Plasma
title_full_unstemmed Novel Gene Fusions in Glioblastoma Tumor Tissue and Matched Patient Plasma
title_short Novel Gene Fusions in Glioblastoma Tumor Tissue and Matched Patient Plasma
title_sort novel gene fusions in glioblastoma tumor tissue and matched patient plasma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281415/
https://www.ncbi.nlm.nih.gov/pubmed/32414213
http://dx.doi.org/10.3390/cancers12051219
work_keys_str_mv AT wanglan novelgenefusionsinglioblastomatumortissueandmatchedpatientplasma
AT yekulaanudeep novelgenefusionsinglioblastomatumortissueandmatchedpatientplasma
AT muralidharankoushik novelgenefusionsinglioblastomatumortissueandmatchedpatientplasma
AT smalljulial novelgenefusionsinglioblastomatumortissueandmatchedpatientplasma
AT roshzacharys novelgenefusionsinglioblastomatumortissueandmatchedpatientplasma
AT kangkeikom novelgenefusionsinglioblastomatumortissueandmatchedpatientplasma
AT carterbobs novelgenefusionsinglioblastomatumortissueandmatchedpatientplasma
AT balajleonora novelgenefusionsinglioblastomatumortissueandmatchedpatientplasma