Analysis of CDKN2A gene alterations in recurrent and non-recurrent meningioma

Guyot, Anne; Duchesne, Mathilde; Robert, Sandrine; Lia, Anne‐Sophie; Derouault, Paco; Scaon, Erwan; Lemnos, Leslie; Salle, Henri; Durand, Karine; Labrousse, François

doi:10.1007/s11060-019-03333-6

Cited by 54 publications

(46 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Such an adverse outcome is in line with the reported association between CDKN2A/B homozygous deletion and higher recurrence risk of meningiomas [21,43,44]. In a series of 30 cases of variable histotype and grade, the homozygous deletion of CDKN2A/B was identified in three anaplastic (grade III) meningiomas with ≥ 20 mitoses/10 HPF and that recurred [43]. Our findings show that CDKN2A/B homozygous deletion can be also found in atypical meningiomas, in the absence of a high mitotic index.…”

Section: Discussionsupporting

confidence: 84%

Molecular Profiling of 22 Primary Atypical Meningiomas Shows the Prognostic Significance of 18q Heterozygous Loss and CDKN2A/B Homozygous Deletion on Recurrence-Free Survival

Barresi

Simbolo

Fioravanzo

et al. 2021

Cancers

View full text Add to dashboard Cite

The use of adjuvant therapy is controversial in atypical meningiomas with gross total resection. Predictors of recurrence risk could be useful in selecting patients for additional treatments. The aim of this study was to investigate whether molecular features are associated with recurrence risk of atypical meningiomas. According to WHO classification, the diagnosis of atypical meningioma was based on the presence of one major criteria (mitotic activity, brain invasion) or three or more minor criteria. The molecular profile of 22 cases (eight mitotically active, eight brain-invasive, and six with minor criteria) was assessed exploring the mutational status and copy number variation of 409 genes using next generation sequencing. Of the 22 patients with a median follow up of 53.5 months, 13 had recurrence of disease within 68 months. NF2 mutation was the only recurrent alteration (11/22) and was unrelated to clinical-pathological features. Recurring meningiomas featured a significantly higher proportion of copy number losses than non-recurring ones (p = 0.027). Chromosome 18q heterozygous loss or CDKN2A/B homozygous deletion was significantly associated with shorter recurrence-free survival (p = 0.008; hazard ratio: 5.3). Atypical meningiomas could be tested routinely for these genetic alterations to identify cases for adjuvant treatment.

show abstract

Section: Discussionsupporting

confidence: 84%

Molecular Profiling of 22 Primary Atypical Meningiomas Shows the Prognostic Significance of 18q Heterozygous Loss and CDKN2A/B Homozygous Deletion on Recurrence-Free Survival

Barresi

Simbolo

Fioravanzo

et al. 2021

Cancers

View full text Add to dashboard Cite

show abstract

“…Most high-grade meningiomas show a highly perturbed copy number profile and they are enriched for TERT promoter mutations [ 6 , 7 , 11 , 12 ]. In addition, homozygous focal deletions of the cyclin-dependent kinase inhibitor 2A ( CDKN2A ) gene, located at 9p21, have been observed at high frequency in anaplastic meningiomas [ 1 , 3 , 4 , 9 , 13 ]. An association of chromosome 9p21 deletion with malignant progression of meningiomas and poor prognosis, specifically in anaplastic meningiomas, has been demonstrated in 2002 by Perry et al [ 9 ].…”

mentioning

confidence: 99%

CDKN2A/B homozygous deletion is associated with early recurrence in meningiomas

et al. 2020

View full text Add to dashboard Cite

“…Meningioma is a genetic disease that is common in patients with neurofibromatosis type 2, a complex autosomal disorder caused by germline heterozygous loss of function mutations in the tumor suppressor NF2 7 . While NF2 mutations are also common in sporadic meningiomas 8,9 , clinically actionable somatic variants in meningiomas are rare and generally not associated with adverse outcomes [10][11][12][13][14][15][16][17][18][19] , with infrequent exceptions 20,21 . Classification of meningiomas based on DNA methylation predicts outcomes better than somatic variants or histologic grade 15,19,22,23 , but DNA methylation profiles have not elucidated biologic drivers or targets for molecular therapy to treat meningioma patients.…”

mentioning

confidence: 99%

Multiplatform genomic profiling and magnetic resonance imaging identify mechanisms underlying intratumor heterogeneity in meningioma

et al. 2020

View full text Add to dashboard Cite

Meningiomas are the most common primary intracranial tumors, but the molecular drivers of meningioma tumorigenesis are poorly understood. We hypothesized that investigating intratumor heterogeneity in meningiomas would elucidate biologic drivers and reveal new targets for molecular therapy. To test this hypothesis, here we perform multiplatform molecular profiling of 86 spatially-distinct samples from 13 human meningiomas. Our data reveal that regional alterations in chromosome structure underlie clonal transcriptomic, epigenomic, and histopathologic signatures in meningioma. Stereotactic co-registration of sample coordinates to preoperative magnetic resonance images further suggest that high apparent diffusion coefficient (ADC) distinguishes meningioma regions with proliferating cells enriched for developmental gene expression programs. To understand the function of these genes in meningioma, we develop a human cerebral organoid model of meningioma and validate the high ADC marker genes CDH2 and PTPRZ1 as potential targets for meningioma therapy using live imaging, single cell RNA sequencing, CRISPR interference, and pharmacology.

show abstract

Analysis of CDKN2A gene alterations in recurrent and non-recurrent meningioma

Cited by 54 publications

References 39 publications

Molecular Profiling of 22 Primary Atypical Meningiomas Shows the Prognostic Significance of 18q Heterozygous Loss and CDKN2A/B Homozygous Deletion on Recurrence-Free Survival

Molecular Profiling of 22 Primary Atypical Meningiomas Shows the Prognostic Significance of 18q Heterozygous Loss and CDKN2A/B Homozygous Deletion on Recurrence-Free Survival

CDKN2A/B homozygous deletion is associated with early recurrence in meningiomas

Multiplatform genomic profiling and magnetic resonance imaging identify mechanisms underlying intratumor heterogeneity in meningioma

Contact Info

Product

Resources

About