Glioblastoma, IDH-Wildtype

This study analyzed 159 patients with secondary glioblastoma (sGBM) and confirmed that the PTPRZ1-MET fusion is a recurrent oncogenic driver associated with significantly shorter overall and progression-free survival. Researchers identified 359 upregulated genes in fusion-positive tumors, enriched in cell-cycle regulation pathways. An artificial intelligence-based diagnostic model, utilizing a three-gene panel (MET, PCDHGA3, FAM3C), was developed and validated to identify this fusion. This robust molecular signature could facilitate the identification and stratification of sGBM patients positive for the PTPRZ1-MET fusion.

This study established 18 patient-derived glioblastoma organoid (GBO) lines that faithfully preserve the histopathological and genomic features of parental tumors. Glioblastoma organoid-based drug sensitivity testing (GBO-DST) demonstrated a strong correlation with progression-free survival and proved superior to MGMT methylation status in predicting temozolomide response. Transcriptomic analysis elucidated mechanisms of temozolomide resistance, including mismatch repair deficiency and elevated MGMT expression. Furthermore, FDA-approved drug screening using GBO-DST identified regorafenib and lazertinib as effective therapeutic alternatives, with lazertinib showing superior efficacy in a GBO transplantation mouse model. These findings highlight the significant potential of GBO-DST as a robust platform for precision oncology in glioblastoma.

This single-center retrospective study investigated the prognostic impact of MGMT promoter methylation and TERT promoter mutations in 54 patients with WHO grade 4 glioblastoma. The findings indicate that MGMT methylation is independently associated with improved overall survival, whereas TERT mutations predict worse survival. Adjuvant chemoradiotherapy was also confirmed to improve outcomes. A combined stratification using both biomarkers allows for the identification of four distinct prognostic subgroups, with MGMT-methylated/TERT-wild-type patients exhibiting the longest survival.

This study compared clinical characteristics and survival between molecularly defined IDH-wild-type glioblastoma (MolGBM) and histologically defined IDH-wild-type glioblastoma (HistGBM). It also characterized lower-grade IDH-wild-type astrocytic tumors lacking glioblastoma-defining genomic alterations. MolGBM exhibited a more favorable adjusted overall survival (HR 0.40) compared to HistGBM, particularly in patients aged 60 years or older. These findings highlight the clinical and biological heterogeneity among molecularly defined IDH-wild-type diffuse gliomas and the critical role of comprehensive molecular characterization. Lower-grade IDH-wild-type astrocytic tumors without glioblastoma-defining alterations warrant further in-depth molecular investigation.