Abstract
Background. RNAs within extracellular vesicles (EVs) have potential as diagnostic biomarkers for patients with cancer and are identified in a variety of biofluids. Glioblastomas (GBMs) release EVs containing RNA into cerebrospinal fluid (CSF). Here we describe a multi-institutional study of RNA extracted from CSF-derived EVs of GBM patients to detect the presence of tumor-Associated amplifications and mutations in epidermal growth factor receptor (EGFR). Methods. CSF and matching tumor tissue were obtained from patients undergoing resection of GBMs. We determined wild-Type (wt)EGFR DNA copy number amplification, as well as wtEGFR and EGFR variant (v)III RNA expression in tumor samples. We also characterized wtEGFR and EGFRvIII RNA expression in CSF-derived EVs. Results. EGFRvIII-positive tumors had significantly greater wtEGFR DNA amplification (P = 0.02) and RNA expression (P = 0.03), and EGFRvIII-positive CSF-derived EVs had significantly more wtEGFR RNA expression (P = 0.004). EGFRvIII was detected in CSF-derived EVs for 14 of the 23 EGFRvIII tissue-positive GBM patients. Conversely, only one of the 48 EGFRvIII tissue-negative patients had the EGFRvIII mutation detected in their CSF-derived EVs. These results yield a sensitivity of 61% and a specificity of 98% for the utility of CSF-derived EVs to detect an EGFRvIIIpositive GBM. Conclusion. Our results demonstrate CSF-derived EVs contain RNA signatures reflective of the underlying molecular genetic status of GBMs in terms of wtEGFR expression and EGFRvIII status. The high specificity of the CSF-derived EV diagnostic test gives us an accurate determination of positive EGFRvIII tumor status and is essentially a less invasive "liquid biopsy" that might direct mutation-specific therapies for GBMs.
Original language | English (US) |
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Pages (from-to) | 1494-1502 |
Number of pages | 9 |
Journal | Neuro-oncology |
Volume | 19 |
Issue number | 11 |
DOIs | |
State | Published - Nov 1 2017 |
Externally published | Yes |
Keywords
- Biomarker
- CSF
- EGFRvIII
- Glioma
- Vesicle
ASJC Scopus subject areas
- Oncology
- Clinical Neurology
- Cancer Research