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Detection of wild-type EGFR amplification and EGFRvIII mutation in CSF-derived extracellular vesicles of glioblastoma patients.
Figueroa, Javier M; Skog, Johan; Akers, Johnny; Li, Hongying; Komotar, Ricardo; Jensen, Randy; Ringel, Florian; Yang, Isaac; Kalkanis, Steven; Thompson, Reid; LoGuidice, Lori; Berghoff, Emily; Parsa, Andrew; Liau, Linda; Curry, William; Cahill, Daniel; Bettegowda, Chetan; Lang, Frederick F; Chiocca, E Antonio; Henson, John; Kim, Ryan; Breakefield, Xandra; Chen, Clark; Messer, Karen; Hochberg, Fred; Carter, Bob S.
Afiliação
  • Figueroa JM; Division of Neurosurgery and Division of Biostatistics, University of California San Diego (UCSD), San Diego, California, USA; Exosome Diagnostics, Inc, New York, New York, USA; Department of Neurosurgery, University of Miami, Miami, Florida, USA; Department of Neurosurgery, University of Utah, Salt
  • Skog J; Division of Neurosurgery and Division of Biostatistics, University of California San Diego (UCSD), San Diego, California, USA; Exosome Diagnostics, Inc, New York, New York, USA; Department of Neurosurgery, University of Miami, Miami, Florida, USA; Department of Neurosurgery, University of Utah, Salt
  • Akers J; Division of Neurosurgery and Division of Biostatistics, University of California San Diego (UCSD), San Diego, California, USA; Exosome Diagnostics, Inc, New York, New York, USA; Department of Neurosurgery, University of Miami, Miami, Florida, USA; Department of Neurosurgery, University of Utah, Salt
  • Li H; Division of Neurosurgery and Division of Biostatistics, University of California San Diego (UCSD), San Diego, California, USA; Exosome Diagnostics, Inc, New York, New York, USA; Department of Neurosurgery, University of Miami, Miami, Florida, USA; Department of Neurosurgery, University of Utah, Salt
  • Komotar R; Division of Neurosurgery and Division of Biostatistics, University of California San Diego (UCSD), San Diego, California, USA; Exosome Diagnostics, Inc, New York, New York, USA; Department of Neurosurgery, University of Miami, Miami, Florida, USA; Department of Neurosurgery, University of Utah, Salt
  • Jensen R; Division of Neurosurgery and Division of Biostatistics, University of California San Diego (UCSD), San Diego, California, USA; Exosome Diagnostics, Inc, New York, New York, USA; Department of Neurosurgery, University of Miami, Miami, Florida, USA; Department of Neurosurgery, University of Utah, Salt
  • Ringel F; Division of Neurosurgery and Division of Biostatistics, University of California San Diego (UCSD), San Diego, California, USA; Exosome Diagnostics, Inc, New York, New York, USA; Department of Neurosurgery, University of Miami, Miami, Florida, USA; Department of Neurosurgery, University of Utah, Salt
  • Yang I; Division of Neurosurgery and Division of Biostatistics, University of California San Diego (UCSD), San Diego, California, USA; Exosome Diagnostics, Inc, New York, New York, USA; Department of Neurosurgery, University of Miami, Miami, Florida, USA; Department of Neurosurgery, University of Utah, Salt
  • Kalkanis S; Division of Neurosurgery and Division of Biostatistics, University of California San Diego (UCSD), San Diego, California, USA; Exosome Diagnostics, Inc, New York, New York, USA; Department of Neurosurgery, University of Miami, Miami, Florida, USA; Department of Neurosurgery, University of Utah, Salt
  • Thompson R; Division of Neurosurgery and Division of Biostatistics, University of California San Diego (UCSD), San Diego, California, USA; Exosome Diagnostics, Inc, New York, New York, USA; Department of Neurosurgery, University of Miami, Miami, Florida, USA; Department of Neurosurgery, University of Utah, Salt
  • LoGuidice L; Division of Neurosurgery and Division of Biostatistics, University of California San Diego (UCSD), San Diego, California, USA; Exosome Diagnostics, Inc, New York, New York, USA; Department of Neurosurgery, University of Miami, Miami, Florida, USA; Department of Neurosurgery, University of Utah, Salt
  • Berghoff E; Division of Neurosurgery and Division of Biostatistics, University of California San Diego (UCSD), San Diego, California, USA; Exosome Diagnostics, Inc, New York, New York, USA; Department of Neurosurgery, University of Miami, Miami, Florida, USA; Department of Neurosurgery, University of Utah, Salt
  • Parsa A; Division of Neurosurgery and Division of Biostatistics, University of California San Diego (UCSD), San Diego, California, USA; Exosome Diagnostics, Inc, New York, New York, USA; Department of Neurosurgery, University of Miami, Miami, Florida, USA; Department of Neurosurgery, University of Utah, Salt
  • Liau L; Division of Neurosurgery and Division of Biostatistics, University of California San Diego (UCSD), San Diego, California, USA; Exosome Diagnostics, Inc, New York, New York, USA; Department of Neurosurgery, University of Miami, Miami, Florida, USA; Department of Neurosurgery, University of Utah, Salt
  • Curry W; Division of Neurosurgery and Division of Biostatistics, University of California San Diego (UCSD), San Diego, California, USA; Exosome Diagnostics, Inc, New York, New York, USA; Department of Neurosurgery, University of Miami, Miami, Florida, USA; Department of Neurosurgery, University of Utah, Salt
  • Cahill D; Division of Neurosurgery and Division of Biostatistics, University of California San Diego (UCSD), San Diego, California, USA; Exosome Diagnostics, Inc, New York, New York, USA; Department of Neurosurgery, University of Miami, Miami, Florida, USA; Department of Neurosurgery, University of Utah, Salt
  • Bettegowda C; Division of Neurosurgery and Division of Biostatistics, University of California San Diego (UCSD), San Diego, California, USA; Exosome Diagnostics, Inc, New York, New York, USA; Department of Neurosurgery, University of Miami, Miami, Florida, USA; Department of Neurosurgery, University of Utah, Salt
  • Lang FF; Division of Neurosurgery and Division of Biostatistics, University of California San Diego (UCSD), San Diego, California, USA; Exosome Diagnostics, Inc, New York, New York, USA; Department of Neurosurgery, University of Miami, Miami, Florida, USA; Department of Neurosurgery, University of Utah, Salt
  • Chiocca EA; Division of Neurosurgery and Division of Biostatistics, University of California San Diego (UCSD), San Diego, California, USA; Exosome Diagnostics, Inc, New York, New York, USA; Department of Neurosurgery, University of Miami, Miami, Florida, USA; Department of Neurosurgery, University of Utah, Salt
  • Henson J; Division of Neurosurgery and Division of Biostatistics, University of California San Diego (UCSD), San Diego, California, USA; Exosome Diagnostics, Inc, New York, New York, USA; Department of Neurosurgery, University of Miami, Miami, Florida, USA; Department of Neurosurgery, University of Utah, Salt
  • Kim R; Division of Neurosurgery and Division of Biostatistics, University of California San Diego (UCSD), San Diego, California, USA; Exosome Diagnostics, Inc, New York, New York, USA; Department of Neurosurgery, University of Miami, Miami, Florida, USA; Department of Neurosurgery, University of Utah, Salt
  • Breakefield X; Division of Neurosurgery and Division of Biostatistics, University of California San Diego (UCSD), San Diego, California, USA; Exosome Diagnostics, Inc, New York, New York, USA; Department of Neurosurgery, University of Miami, Miami, Florida, USA; Department of Neurosurgery, University of Utah, Salt
  • Chen C; Division of Neurosurgery and Division of Biostatistics, University of California San Diego (UCSD), San Diego, California, USA; Exosome Diagnostics, Inc, New York, New York, USA; Department of Neurosurgery, University of Miami, Miami, Florida, USA; Department of Neurosurgery, University of Utah, Salt
  • Messer K; Division of Neurosurgery and Division of Biostatistics, University of California San Diego (UCSD), San Diego, California, USA; Exosome Diagnostics, Inc, New York, New York, USA; Department of Neurosurgery, University of Miami, Miami, Florida, USA; Department of Neurosurgery, University of Utah, Salt
  • Hochberg F; Division of Neurosurgery and Division of Biostatistics, University of California San Diego (UCSD), San Diego, California, USA; Exosome Diagnostics, Inc, New York, New York, USA; Department of Neurosurgery, University of Miami, Miami, Florida, USA; Department of Neurosurgery, University of Utah, Salt
  • Carter BS; Division of Neurosurgery and Division of Biostatistics, University of California San Diego (UCSD), San Diego, California, USA; Exosome Diagnostics, Inc, New York, New York, USA; Department of Neurosurgery, University of Miami, Miami, Florida, USA; Department of Neurosurgery, University of Utah, Salt
Neuro Oncol ; 19(11): 1494-1502, 2017 Oct 19.
Article em En | MEDLINE | ID: mdl-28453784
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 EGFRvIII-positive 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.
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Texto completo: 1 Coleções: 01-internacional Temas: Geral / Tipos_de_cancer / Outros_tipos Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Amplificação de Genes / Glioblastoma / Receptores ErbB / Vesículas Extracelulares / Mutação Tipo de estudo: Diagnostic_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Neuro Oncol Assunto da revista: NEOPLASIAS / NEUROLOGIA Ano de publicação: 2017 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Temas: Geral / Tipos_de_cancer / Outros_tipos Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Amplificação de Genes / Glioblastoma / Receptores ErbB / Vesículas Extracelulares / Mutação Tipo de estudo: Diagnostic_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Neuro Oncol Assunto da revista: NEOPLASIAS / NEUROLOGIA Ano de publicação: 2017 Tipo de documento: Article