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15.11.2019 | Laboratory Investigation

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

verfasst von: Anne Guyot, Mathilde Duchesne, Sandrine Robert, Anne-Sophie Lia, Paco Derouault, Erwan Scaon, Leslie Lemnos, Henri Salle, Karine Durand, François Labrousse

Erschienen in: Journal of Neuro-Oncology | Ausgabe 3/2019

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Abstract

Purpose

Assessment of the risk of recurrence is essential to determine the therapeutic strategy of meningioma treatment. Many relapsing or aggressive meningiomas show elevated mitotic and/or Ki67 indices, reflecting cell cycle deregulation. As CDKN2A is a key tumor suppressor gene involved in cell cycle control, we investigated whether CDKN2A alterations may be involved in tumor recurrence.

Methods

We carried out a comparative analysis of 17 recurrent and 13 non-recurrent meningiomas. CDKN2A single nucleotide variations (SNVs), deletions, methylation status of the promotor, and p16 expression were investigated. Results were correlated with the recurrent or non-recurrent status and clinicopathological data.

Results

We identified a CDKN2A SNV (NM_000077, exon2, c.G442A, p.Ala148Thr) in five meningiomas that was significantly associated with recurrence (p = 0.03). This mutation, confirmed by Sanger sequencing and referenced in the COSMIC database in various cancers, has not been reported in meningioma. The presence of one of the three following CDKN2A alterations—p.(Ala148Thr) mutation, whole homozygous or heterozygous gene loss, or promotor methylation > 8%—was observed in 13 of the 17 relapsing meningiomas and was strongly associated with recurrence (p < 0.0001) and a Ki67 labeling index > 7% (p = 0.004).

Conclusion

We report an undescribed p.(Ala148Thr) CDKN2A mutation in meningioma that was only present in relapsing tumors. In our series, CDKN2A gene alterations were only found in recurrent meningiomas. However, our results need to be evaluated on a larger series to ensure that these CDKN2A alterations can be used as biomarkers of recurrence in meningioma.

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Titel: Analysis of CDKN2A gene alterations in recurrent and non-recurrent meningioma
verfasst von: Anne Guyot
Mathilde Duchesne
Sandrine Robert
Anne-Sophie Lia
Paco Derouault
Erwan Scaon
Leslie Lemnos
Henri Salle
Karine Durand
François Labrousse
Publikationsdatum: 15.11.2019
Verlag: Springer US
Erschienen in: Journal of Neuro-Oncology / Ausgabe 3/2019
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-019-03333-6

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