Abstract
Gliomas represent one of the most lethal cancers in mankind. Glioblastoma, IDH wild-type (CNS WHO grade 4), the most common and most malignant among gliomas, is associated with the worst outcome whereas lower-grade gliomas (CNS WHO grade 2-3), albeit better in survival, display infiltrative growth that prevents complete surgical resection. Residual tumors eventually progress and undergo malignant transformation. Standard therapies include resection, radiation and chemotherapy. Most patients with glioma are relatively young. Therefore, their illness is associated with economic burden in several levels including family, workplace and society. Research that leads to more understanding of pathogenesis and development of novel therapies remains an unmet need. Elucidation of genomic landscape for gliomas in Thai patients may provide more insight in cancer initiation and maintenance and that in turn may lead to precision oncology with more accurate diagnosis, prognostication and precision treatment. In addition, this integrated, multi-dimensional brain cancer genome study may serve as a model for interrogating genome for other common cancers in Thailand. The investigators have collected a total of 32 samples from patients with gliomas. We have extracted and sent DNA and RNA from these samples to NGS facility for WES and RNAseq. We also performed DNA methylation profiling. The data analysis was included in this report. However, to have meaningful results from RNA sequencing, more samples may be needed. We continue to collect tumor samples from glioma patients at Siriraj hospital and future analysis in our largest cohort of gliomas in Thailand may shed some lights on genomic heterogeneity that inform new precision diagnostics and treatment. We have also developed a new testing platform using long-read (nanopore) sequencing technology to identify copy number variation (CNV), which is critically required by the new WHO classification. Our nanopore-derived CNV has excellent concordance against CNV-derived from methylome profiling and exome sequencing with a less costly and time-consuming manner. This study was published in Brain Pathology in August 2023. In addition, we have interrogated tumor microenvironment, i.e. immune cells in various types of gliomas of 10 samples. We demonstrated the feasibility of using the technique and some differences among different types of gliomas were observed. Future validation in larger samples is needed and ongoing.
