Sequencing and curation strategies for identifying candidate glioblastoma treatments

Abstract

Background Prompted by the revolution in high-throughput sequencing and its potential impact for treating cancer patients, we initiated a clinical research study to compare the ability of different sequencing assays and analysis methods to analyze glioblastoma tumors and generate real-time potential treatment options for physicians. Methods A consortium of seven institutions in New York City enrolled 30 patients with glioblastoma and performed tumor whole genome sequencing (WGS) and RNA sequencing (RNA-seq; collectively WGS/RNA-seq); 20 of these patients were also analyzed with independent targeted panel sequencing. We also compared results of expert manual annotations with those from an automated annotation system, Watson Genomic Analysis (WGA), to assess the reliability and time required to identify potentially relevant pharmacologic interventions. Results WGS/RNAseq identified more potentially actionable clinical results than targeted panels in 90% of cases, with an average of 16-fold more unique potentially actionable variants identified per individual; 84 clinically actionable calls were made using WGS/RNA-seq that were not identified by panels. Expert annotation and WGA had good agreement on identifying variants [mean sensitivity = 0.71, SD = 0.18 and positive predictive value (PPV) = 0.80, SD = 0.20] and drug targets when the same variants were called (mean sensitivity = 0.74, SD = 0.34 and PPV = 0.79, SD = 0.23) across patients. Clinicians used the information to modify their treatment plan 10% of the time. Conclusion These results present the first comprehensive comparison of technical and machine augmented analysis of targeted panel and WGS/RNA-seq to identify potential cancer treatments.

Correlation of immunohistochemical expression of HIF-1alpha and IDH1 with clinicopathological and therapeutic data of moroccan glioblastoma and survival analysis

“…Despite the fundamental knowledge about glioblastoma biology and the new generation of genetic sequencing “NGS”, these tumours are difficult to treat because of their inter-tumoral and intra-tumoral heterogeneity. Currently available treatments can only slow progression and reduce clinical signs and symptoms [ [26] , [27] , [28] , [29] , [30] , [31] ].…”

Current status and perspectives of genetic testing in gastrointestinal cancer (Review)

“…A recent genomic-based study of glioblastoma patients examined the usefulness of WGS/RNA-seq vs. targeted panels ( 106 ). WGS/RNA-seq detected more conceivably criminal clinical findings than targeted panels in 90% of cases, with an average of 16-fold more unique conceivably criminal variants identified for each patient.…”

Clinical Application of Next-Generation Sequencing in Recurrent Glioblastoma

“…This type of precision medicine is appealing, but it has not so easily translated to patients with recurrent GBM due to lack of robust biomarker-enriched clinical studies showing benefit beyond the standard of care. It is notable that the routine sequencing of patients with recurrent GBM has not been widely adopted and data utilization for clinical actionability can vary [10]. Additionally, the cost of NGS can be prohibitive, further making widespread adoption difficult [11].…”