Chromosome 1p Loss and 1q Gain for Grading of Meningioma

Importance: The World Health Organization (WHO) classification of central nervous system tumors (CNS) grading for meningioma was updated in 2021 to include rare molecular features, namely homozygous deletions of CDKN2A or CDKN2B and TERT promotor alterations. Previous work, including the cIMPACT-NOW statement, has discussed the potential value of including chromosomal copy number alterations to help refine the current grading system. Objective: To identify chromosomal copy number alterations that could be used to improve the current CNS WHO grading of meningioma. Design, Setting, and Participants: In this cohort study, patients with surgically treated meningioma were followed-up until recurrence or progression of disease or death. Chromosomal copy number alterations were then correlated with progression-free survival (PFS) to identify new outcome biomarkers. This study included patients with a histopathological diagnosis of meningioma from multiple institutions in Canada, the US, and Germany, with molecular data collection starting in 2016. Data were analyzed from January to September 2024. Exposures: All patients underwent surgery for meningioma and a subset underwent radiation therapy. Main Outcomes and Measures: The main outcome was PFS. Cox regression analysis was used to identify copy number alterations associated with outcomes in the context of WHO grading. Results: Among 1964 patients with meningioma (1256 female; median [IQR] age, 58 [48-69] years) assessed, loss of chromosome 1p in WHO grade 1 meningiomas was associated with significantly worse outcomes compared with tumors without loss of 1p (median PFS, 5.83 [95% CI, 4.36-∞] years vs 34.54 [95% CI, 16.01-∞] years; log-rank P <.001). Outcomes of patients with WHO grade 1 tumors with loss of chromosome 1p were comparable to those of patients with WHO grade 2 tumors (median PFS, 4.48 [95% CI, 4.09-5.18] years). Combined loss of chromosome 1p and gain of chromosome 1q were associated with outcomes that were highly concordant with WHO grade 3 tumors, regardless of initial grade (median PFS: grade 1, 2.23 [95% CI, 1.28-∞] years; grade 2, 1.90 [95% CI, 1.23-2.25] years; grade 3, 2.27 [95% CI, 1.68-3.05] years). Conclusions and Relevance: These findings highlight a role for cytogenetic profiling in the next iteration of CNS WHO grading, with a specific focus on chromosome 1p loss and 1q gain, suggesting that chromosome 1p loss, in addition to 22q loss, should be added as a criterion for a CNS WHO grade of 2 and addition of 1q gain as a criterion for a CNS WHO grade of 3..