Abstract

Circulating biomarkers in blood may provide an interesting alternative to risky tissue biopsies in the diagnosis and follow-up of glioblastoma patients. We have assessed MGMT methylation status in blood and tissue samples from unresected glioblastoma patients who had been included in the randomized GENOM-009 trial. Paired blood and tissue samples were assessed by methylation-specific PCR (MSP) and pyrosequencing (PYR). After establishing the minimum PYR cut-off that could yield a significant difference in overall survival, we assessed the sensitivity, specificity, positive predictive value and negative predictive value (NPV) of the analyses. Methylation could be detected in cfDNA by both MSP and PYR but with low concordance with results in tissue. Sensitivity was low for both methods (31% and 38%, respectively), while specificity was higher for MSP in blood than for PYR in plasma (96% vs 76%) and NPV was similar (56 vs 57%). Concordance of results in tissue by MSP and PYR was 84.3% (P < 0.001) and correlated with outcome. We conclude that detection of cfDNA in the blood of glioblastoma patients can be an alternative when tumor tissue is not available but methods for the detection of cfDNA in blood must improve before it can replace analysis in tumor tissue.

Details

Title
Pyrosequencing versus methylation-specific PCR for assessment of MGMT methylation in tumor and blood samples of glioblastoma patients
Author
Estival, Anna 1 ; Sanz, Carolina 2 ; Ramirez, Jose-Luis 1 ; Velarde, Jose Maria 3 ; Domenech, Marta 1 ; Carrato, Cristina 2 ; Ramón de las Peñas 4 ; Gil-Gil, Miguel 5 ; Sepúlveda, Juan 6 ; Armengol, Roser 7 ; Cardiel, Isaac 7 ; Berrocal, Alfonso 8 ; Luque, Raquel 9 ; Herrero, Ana 10 ; Balana, Carmen 1   VIAFID ORCID Logo 

 Medical Oncology Service, Catalan Institute of Oncology Badalona, Hospital Germans Trias i Pujol, Applied Research Group in Oncology (B-ARGO Group), Badalona, Spain 
 Pathology Service, University Hospital Germans Trias i Pujol, Badalona, Spain 
 Statistical Unit, Applied Research Group in Oncology (B-ARGO Group), Institut Investigació Germans Trias i Pujol (IGTP), Badalona, Spain 
 Medical Oncology Service, Hospital Provincial de Castellón, Castellón, Spain 
 Medical Oncology Service, Catalan Institute of Oncology l’Hospitalet de LLobregat, Bellvitge Biomedical Research Institute (IDIBELL) l’Hospitalet de Llobregat, Barcelona, Spain 
 Medical Oncology Service, University Hospital 12 de Octubre, Madrid, Spain 
 Neurosurgery Service, Hospital Germans Trias i Pujol, Badalona, Spain 
 Medical Oncology Service, University Hospital General de Valencia, Valencia, Spain 
 Medical Oncology Service, University Hospital Virgen de las Nieves, Granada, Spain 
10  Medical Oncology Service, Hospital Miguel Servet, Zaragoza, Spain 
Pages
1-12
Publication year
2019
Publication date
Jul 2019
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2267396883
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.