BIOM-59 - Feasibility and utility of the novel cancer comprehensive genomic profiling RNA-seq for the identification of therapeutic targets and diagnostic biomarkers in glioma

Saturday, November 18, 2023

12:00 PM – 12:05 PM PT

Location: Room 118-120

Oral Abstract Presenter(s)

Masamichi Takahashi

Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital
Tokyo, Tokyo, Japan

Author(s)

SK

Shinji Kohsaka

Division of Cellular Signaling, National Cancer Center Research Institute
Tokyo, Tokyo, Japan
KI

Koichi Ichimura

Department of Brain Disease Translational Research, Faculty of Medicine, Juntendo University
Tokyo, Tokyo, Japan
HM

Hiroyuki Mano

National Cancer Center Research Institute
Tokyo, Tokyo, Japan
YOSHITAKA NARITA

National Cancer Center Hospital
Tokyo, Tokyo, Japan

Background: The detection of novel therapeutic targets is increasingly important in oncology. The Todai OncoPanel (TOP) RNA panel is a custom target RNA-seq using the junction capture method to maximize the sensitivity in detecting of known 456 fusion gene transcripts, which is approved in Japan in 2022 and covered by insurance in later 2023. Above, TOP RNA panel interrogates aberrantly spliced transcripts and analyzes the expression profiles of 1,390 genes. Primary brain tumors require various molecular profiles to be classified based on WHO2021 classification and also necessitates new therapeutic targets. In this study, we aimed to classify gliomas and identify the molecular targets by TOP RNA panel.

Methods: Among 131 frozen samples of malignant gliomas, 124 samples passed quality control and were subjected to TOP RNA panel. Fusion detection and RNA expression analysis were conducted with the original pipeline. Cluster analysis and Gene Set Enrichment Analysis (GSEA) were performed to identify gene sets specific for individual subtypes. Copy numbers of tyrosine kinase genes, MDM2 and CDK4 were evaluated by digital droplet PCR (ddPCR).

Results: Among 55 cases of glioblastoma, gene fusions were detected in 11 cases (20.0%) including novel MET fusions, and overexpression of seven tyrosine kinase genes were observed in 15 cases (27.3%). Of the 34 overexpressed genes, gene amplification was observed in 17 genes (50%) by ddPCR. In contrast to IDH-wildtype glioblastoma, IDH-mutant tumors hardly harbored fusion genes or gene overexpression. GSEA identified that the gene sets related to 1p36 and 19q were relatively enriched in astrocytoma, suggesting that regional genomic DNA copy number alterations can be evaluated by gene expression analysis.

Conclusion: TOP RNA panel detects more fusions than DNA panel and is utilized not only for the detection of molecular targets but also for the molecular classification of glioma, providing treatments optimized for the individual patients.