Clinical, molecular characteristics, and telomere-maintaining mechanism of spinal cord glioma with or without H3 K27M mutation: a prognostic and experimental study.

BACKGROUND

Spinal cord gliomas were rare, and their molecular characteristics, pathogenesis, and prognosis remain poorly understood. The 2021 WHO Classification introduced "Diffuse midline glioma, H3 K27-altered" (DMG) as a distinct entity, implicating H3 K27 alterations in DMG pathogenesis. However, molecular distinctions between H3 K27-altered and H3 K27 wild-type spinal cord glioma are underexplored.

METHODS

This single-institution retrospective study analyzed 47 patients with spinal cord glioma stratified by H3 K27M status. Clinical, pathological, and molecular profiles were compared between groups. Telomerase reverse transcriptase expression and alternative lengthening of telomeres (ALT) pathway activity were evaluated independently of H3 K27M status.

RESULTS

H3 K27M mutation and wild-type spinal cord glioma exhibited distinct molecular profiles. Telomere maintenance mechanism was identified in spinal cord glioma and appears to be associated with H3 K27M mutation status. Opposing prognostic effects of telomerase activity and the ALT pathway were observed, highlighting the potential role of ALT in H3 K27M mutation spinal DMG.

CONCLUSIONS

This study is the first to delineate clinical, pathological, and prognostic features of H3 K27-altered spinal cord glioma under the 2021 WHO framework. We clarified the clinical significance of telomere maintenance in H3 K27M mutation spinal cord glioma, highlighting the ALT pathway as a key prognostic mechanism. These findings provide a basis for future research on H3 K27-altered molecules and potential therapeutic strategies.