Article
Frequent inactivating mutations of the PBAF complex gene PBRM1 in meningioma with papillary features
Das Gen PBRM1 ist häufig mit papillärem Meningeomen vergesellschaftet
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Published: | June 4, 2021 |
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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.