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

in JAMA oncology by Alexander P Landry, Justin Z Wang, Vikas Patil, Jeff Liu, Chloe Gui, Yosef Ellenbogen, Andrew Ajisebutu, Leeor Yefet, Qingxia Wei, Olivia Singh, Julio Sosa, Sheila Mansouri, Aaron A Cohen-Gadol, Ghazaleh Tabatabai, Marcos Tatagiba, Felix Behling, Jill S Barnholtz-Sloan, Andrew E Sloan, Silky Chotai, Lola B Chambless, Alireza Mansouri, Serge Makarenko, Stephen Yip, Felix Ehret, David Capper, Derek S Tsang, Jennifer Moliterno, Murat Gunel, Pieter Wesseling, Felix Sahm, Kenneth Aldape, Andrew Gao, Gelareh Zadeh, Farshad Nassiri

TLDR

  • Researchers studied DNA changes in meningioma tumors to identify new biomarkers that could improve the current grading system.
  • They found that loss of chromosome 1p was associated with worse outcomes in WHO grade 1 meningiomas, and combined loss of chromosome 1p and gain of chromosome 1q were associated with outcomes similar to grade 3 tumors.

Abstract

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. To identify chromosomal copy number alterations that could be used to improve the current CNS WHO grading of meningioma. 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. All patients underwent surgery for meningioma and a subset underwent radiation therapy. The main outcome was PFS. Cox regression analysis was used to identify copy number alterations associated with outcomes in the context of WHO grading. 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). 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.

Overview

  • The study aimed to identify chromosomal copy number alterations that could improve the current CNS WHO grading of meningioma.
  • The study included 1964 patients with meningioma from multiple institutions in Canada, the US, and Germany, with molecular data collected starting in 2016.
  • The main outcome was progression-free survival (PFS), and Cox regression analysis was used to identify copy number alterations associated with outcomes in the context of WHO grading.

Comparative Analysis & Findings

  • Loss of chromosome 1p in WHO grade 1 meningiomas was associated with worse outcomes compared to tumors without loss of 1p.
  • Outcomes of patients with WHO grade 1 tumors with loss of chromosome 1p were comparable to those of patients with WHO grade 2 tumors.
  • Combined loss of chromosome 1p and gain of chromosome 1q were associated with outcomes highly concordant with WHO grade 3 tumors, regardless of initial grade.

Implications and Future Directions

  • The findings suggest that chromosome 1p loss and 1q gain should be added as criteria for a CNS WHO grade of 2 and 3, respectively.
  • The study highlights a role for cytogenetic profiling in the next iteration of CNS WHO grading.
  • Future studies should explore the applicability of these findings to other types of CNS tumors and the potential for integrating DNA methylation data into the grading system.
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