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Journal of Neuro-Oncology

, Volume 145, Issue 3, pp 449–459 | Cite as

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

  • Anne Guyot
  • Mathilde Duchesne
  • Sandrine Robert
  • Anne-Sophie Lia
  • Paco Derouault
  • Erwan Scaon
  • Leslie Lemnos
  • Henri Salle
  • Karine Durand
  • François LabrousseEmail author
Laboratory Investigation
  • 78 Downloads

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.

Keywords

Meningioma Meningioma recurrence CDKN2A Next-generation-sequencing Methylation 

Notes

Acknowledgements

We thank the CRBiolim tumor bank collection of the Dupuytren University Hospital, and particularly Mr. Alain Chaunavel, for providing tumor and non-tumor samples and the Hight Throughput Sequencing unit of CHU Dupuytren and the Bioinformatic team of the GEIST Institute for sequencing and bioinformatic analyses. We also thank "La Ligue Contre le Cancer de la Corrèze" and the "Comité d’Organisation de la Recherche Contre le Cancer du Limousin (CORC)" whose grants allowed us to conduct this study.

Supplementary material

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Supplementary file3 (TIFF 11730 kb)
11060_2019_3333_MOESM3_ESM.docx (21 kb)
Supplementary file3 (DOCX 20 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Anne Guyot
    • 1
  • Mathilde Duchesne
    • 1
  • Sandrine Robert
    • 2
  • Anne-Sophie Lia
    • 3
  • Paco Derouault
    • 3
  • Erwan Scaon
    • 4
  • Leslie Lemnos
    • 5
  • Henri Salle
    • 5
  • Karine Durand
    • 1
    • 2
  • François Labrousse
    • 1
    • 2
    Email author
  1. 1.Department of PathologyLimoges University HospitalLimogesFrance
  2. 2.EA 3842, CAPTuR « Contrôle de L’Activation Cellulaire, Progression Tumorale Et Résistance Thérapeutique », Faculty of MedicineLimoges UniversityLimogesFrance
  3. 3.EA 6309, MMNP « Maintenance Myélinique Et Neuropathies Périphériques », Faculty of MedicineLimoges UniversityLimogesFrance
  4. 4.Bioinformatics Unit, BISCEM Platform, CBRSUniversity of LimogesLimogesFrance
  5. 5.Department of NeurosurgeryLimoges University HospitalLimogesFrance

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