IDH1 mutation

P1, N=15, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Aug 2026 --> Dec 2026 | Trial primary completion date: Aug 2026 --> Dec 2026

Performing molecular testing (in the absence of adequate tumor tissue with liquid biopsy) as early as possible is already an integral part of the treatment pathway planning for CCA patients. Early molecular testing may therefore lead to the possibility of administering targeted therapy in the first-line setting within this patient group, pending the outcomes of clinical trials.

P2, N=0, Withdrawn, M.D. Anderson Cancer Center | Trial completion date: Aug 2029 --> Jun 2026 | Trial primary completion date: Aug 2027 --> Jun 2026

Timely neurosurgical intervention, multidisciplinary care, and integrated obstetric-neurosurgical strategies are crucial. There is a pressing need for clinical guidelines addressing high-grade glioma management in pregnancy, particularly in the era of molecular tumor classification.

This study expands the spectrum of RUNX1 fusions and highlights the integral diagnostic value of morphology, flow cytometry, cytogenetics, FISH, and NGS analyses for broad structural variant detection in clinical practice. Furthermore, the truncating mutation in one allele of RUNX1 and RUNX1::ARID1B of the second allele detected with advanced disease suggests the possibility of combined transcriptional and chromatin regulatory alterations in disease recurrence in the patient.

Overall, these data describe subtype-specific patterns of m6A marking and isoform architecture across glioma tissues, derived from computational inference using direct RNA sequencing in a modestly sized cohort and warrant validation by orthogonal methods in larger studies. These findings are consistent with concurrent independent evidence that isoform-specific m6A deposition is evolutionarily conserved across mammals and that long-read isoform resolution reveals transcript diversity in glioma not captured by gene-level analysis. While cohort size and the absence of orthogonal site-level validation suggest that the data require cautious interpretation, this work provides a hypothesis-generating resource and methodological framework for future mechanistic and translational investigation of the glioma epitranscriptome.

Notably, in vitro and in vivo experiments demonstrate that 2-HG induces CDH1 downregulation and reduces quiescent cell populations not only in glioblastoma cells but also in lung cancer and colorectal cancer cells, and consistently sensitizes tumor cells to chemotherapy. Our findings shed light on why IDH1 mutations correlate with better prognosis and highlight the translational potential of 2-HG as a chemotherapy sensitizer.

Compared to supratentorial tumors, non-R132H IDH1 mutations are significantly more frequent in infratentorial tumors. IDH2-mutant gliomas almost exclusively occur in adults and in supratentorial locations, with a significantly higher proportion in oligodendrogliomas than astrocytoma.

Patients with aggressive brain tumors often develop seizures that are difficult to control. In this study, perampanel reduced the number of seizures and did not worsen quality of life, being generally well tolerated. Patient survival was mainly determined by the tumor itself. Larger studies are needed to confirm the drug's effectiveness in reducing seizures, improving quality of life, evaluating survival, and monitoring side effects.

Across both diseases, circulating tumor DNA is emerging as a promising tool for prognostication, minimal residual disease assessment, response monitoring, and early resistance detection. Contemporary care increasingly depends on early molecular profiling, individualized treatment sequencing, and integration of targeted therapies, biomarker-guided immunotherapy, and clinical trials.

This included impaired expression of Cebpe, which encodes a key transcription factor regulating neutrophil differentiation. Reactivation of Cebpe expression, by overexpression of its upstream regulator Cebpa or following treatment with hypomethylating agents restored differentiation, indicating that the differentiation block is reversible.In summary, we found a reversible, pre-leukemic impairment of neutrophil differentiation in IDH1-mutant hematopoiesis that correlates with elevated IDH1 expression in myeloid progenitors and likely explains the strong association of IDH1 mutations with myeloid neoplasms.