gms | German Medical Science

72. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

06.06. - 09.06.2021

Frequent inactivating mutations of the PBAF complex gene PBRM1 in meningioma with papillary features

Das Gen PBRM1 ist häufig mit papillärem Meningeomen vergesellschaftet

Meeting Abstract

  • Priscilla Brastianos - Stephen E. and Catherine Pappas Center for Neuro-Oncology, Division of Hematology/Oncology, Department of Neurology, Boston, MA, Vereinigte Staaten
  • Daniel Cahill - Massachusetts General Hospital Cancer Center, Harvard Medical School, Translational Neuro-Oncology Laboratory, Department of Neurosurgery, Boston, MA, Vereinigte Staaten
  • presenting/speaker Tareq Juratli - Universitätsklinikum Carl Gustav Carus Dresden, Neurochirurgie, Dresden, Deutschland
  • Insa Prilop - Universitätsklinikum Carl Gustav Carus Dresden, Neurochirurgie, Dresden, Deutschland
  • Shakti Ramkissoon - Foundation Medicine Inc Cambridge, Massachusetts General Hospital Cancer Center, Harvard Medical School, Translational Neuro-Oncology Laboratory, Department of Neurosurgery, Boston, MA, Vereinigte Staaten; Wake Forest Comprehensive Cancer Center, Department of Pathology, Winston-Salem, NC, Vereinigte Staaten
  • Sandro Santagata - Brigham and Women’s Hospital, Department of Pathology, Boston, MA, Vereinigte Staaten
  • Erik Williams - Foundation Medicine Inc Cambridge, Massachusetts General Hospital Cancer Center, Harvard Medical School, Translational Neuro-Oncology Laboratory, Department of Neurosurgery, Boston, MA, Vereinigte Staaten

Deutsche Gesellschaft für Neurochirurgie. 72. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgie. sine loco [digital], 06.-09.06.2021. Düsseldorf: German Medical Science GMS Publishing House; 2021. DocP037

doi: 10.3205/21dgnc325, urn:nbn:de:0183-21dgnc3258

Published: June 4, 2021

© 2021 Brastianos et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.


Outline

Text

Objective: Papillary meningioma (PM) is a World Health Organization (WHO) grade III tumor that has been associated with brain invasion and aggressive clinical behavior. The genetic alterations associated with PM remain unclear.

Methods: We mined data collected as part of our clinical comprehensive genomic profiling (CGP) initiative which has to date analyzed 8 PM (> 50% papillary morphology) and 22 meningiomas with focal papillary features (10–50%) amongst 562 meningiomas of other subtypes. CGP was performed on hybridization-captured, adaptor ligation-based libraries to a mean coverage depth of > 650 × for 236 or 315 genes plus the introns from 19 or 28 genes frequently involved in cancer.

Results: In our cohort of eight PMs, we identified three cases with inactivation of PBRM1. Of the 22 meningiomas with only focal papillary features, 8 cases were PBRM1-mutant. Thus, 11 of 30 cases with at least focal papillary morphology had inactivation of PBRM1. In the entire cohort of 562 meningiomas that represents a general population of all WHO grades, we identified five additional cases with inactivating alterations in PBRM1 that did not display overt papillary morphology. Thus, 11 of 16 PBRM1-mutant cases (69%) occurred in meningioma with papillary histologic features, supporting a significant association between papillary features and PBRM1 mutation (p < 0.0001). Among the 16 PBRM1-mutant cases (2.8% of cohort), the detected PBRM1 alterations included six intragenic deletions, four frame-shifting insertions, four frame-shifting deletions, and two truncating mutations. All showed biallelic inactivation by SNP array analysis and mutant allele read count data analysis. The majority of PBRM1-mutant meningiomas occurred in female patients (n = 10/16, 62.5%), and median age was 51 years. Most cases were located supratentorially (n = 10).

Conclusion: We identify the tumor suppressor gene PBRM1 as a recurrently altered gene in meningiomas with papillary histomorphology. Further investigational studies are needed to determine whether PBRM1 mutations are an independent negative prognostic biomarker.