Molecular Genetic Profile of 300 Japanese Patients with Diffuse Gliomas Using a Glioma-tailored Gene Panel

Abstract

Rapid technological advances in molecular biology, including next-generation sequencing, have identified key genetic alterations in central nervous system (CNS) tumors. Accordingly, the fifth edition of the World Health Organization (WHO) CNS tumor classification was published in 2021. We analyzed 303 patients with diffuse glioma using an amplicon-based glioma-tailored gene panel for detecting 1p/ 19q codeletion and driver gene mutations such as IDH1/2, TERTp, EGFR, and CDKN2A/B on a single platform. Within glioblastomas (GBMs), the most commonly mutated genes were TERTp, TP53, PTEN, NF1, and PDGFRA, which was the most frequently mutated tyrosine kinase receptor in GBM, followed by EGFR. The genes that most commonly showed evidence of loss were PTEN, CDKN2A/B, and RB1, whereas the genes that most commonly showed evidence of gain/amplification were EGFR, PDGFRA, and CDK4. In 22 grade III oligodendroglial tumors, 3 (14%) patients had CDKN2A/B homozygous deletion, and 4 (18%) patients had ARID1A mutation. In grade III oligodendroglial tumors, an ARID1A mutation was associated with worse progression-free survival. Reclassification based on the WHO 2021 classification resulted in 62.5% of grade II/III isocitrate dehydrogenase (IDH)-wildtype astrocytomas being classified as IDH-wildtype GBM and 37.5% as not elsewhere classified. In summary, our gliomatailored gene panel was applicable for molecular diagnosis in the WHO 2021 classification. In addition, we successfully reclassified the 303 diffuse glioma cases based on the WHO 2021 classification and clarified the genetic profile of diffuse gliomas in the Japanese population.

Genetic mutation patterns among glioblastoma patients in the Taiwanese population – insights from a single institution retrospective study

“…However, this trend is not commonly seen in Chinese patients [ 4 ]. Similarly, Nayuta HIGA et al [ 21 ], utilizing NGS, reported a lower rate of EGFR amplification in GBM in Asian patients compared to those in other regions. Our research confirms a low frequency of EGFR gene mutations in both Groups A and B of our study.…”

Deep‐targeted gene sequencing reveals ARID1A mutation as an important driver of glioblastoma

“… 15 , 16 In cancer, dysfunctional SWI/SNF complexes are intimately associated with tumor development and progression. 17 In gliomas, ARID1A mutations in WHO grade 3 oligodendrocyte tumors are linked to poorer progression‐free survival, 18 yet the role of ARID1A in GBM remains to be fully unraveled.…”

Genetic Mutation Patterns Among Glioblastoma Patients in the Taiwanese Population – Insights from a Single Institution Retrospective Study

“…In the "classic" TCGA (The Cancer Genome Atlas) subtype, there is typically a high frequency of EGFR ampli cation [18], but this is not prevalent in Chinese patients [4]. Another team, Nayuta HIGA et al, [19] using NGS, also reported a lower ampli cation rate of EGFR in GBM in Asian patients compared to other regions. Our experimental results indicate a low frequency of EGFR gene mutations in Groups A and B.…”