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Transcriptome signatures associated with meningioma progression.

ABSTRACT: Meningiomas are the most common primary brain tumor of adults. The majority are benign (WHO grade I), with a mostly indolent course; 20% of them (WHO grade II and III) are, however, considered aggressive and require a more complex management. WHO grade II and III tumors are heterogeneous and, in some cases, can develop from a prior lower grade meningioma, although most arise de novo. Mechanisms leading to progression or implicated in de novo grade II and III tumorigenesis are poorly understood. RNA-seq was used to profile the transcriptome of grade I, II, and III meningiomas and to identify genes that may be involved in progression. Bioinformatic analyses showed that grade I meningiomas that progress to a higher grade are molecularly different from those that do not. As such, we identify GREM2, a regulator of the BMP pathway, and the snoRNAs SNORA46 and SNORA48, as being significantly reduced in meningioma progression. Additionally, our study has identified several novel fusion transcripts that are differentially present in meningiomas, with grade I tumors that did not progress presenting more fusion transcripts than all other tumors. Interestingly, our study also points to a difference in the tumor immune microenvironment that correlates with histopathological grade.

SUBMITTER: Viaene AN

PROVIDER: S-EPMC6489307 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Transcriptome signatures associated with meningioma progression.

Viaene Angela N AN Zhang Bo B Martinez-Lage Maria M Xiang Chaomei C Tosi Umberto U Thawani Jayesh P JP Gungor Busra B Zhu Yuankun Y Roccograndi Laura L Zhang Logan L Bailey Robert L RL Storm Phillip B PB O'Rourke Donald M DM Resnick Adam C AC Grady M Sean MS Dahmane Nadia N

Acta neuropathologica communications 20190430 1

Meningiomas are the most common primary brain tumor of adults. The majority are benign (WHO grade I), with a mostly indolent course; 20% of them (WHO grade II and III) are, however, considered aggressive and require a more complex management. WHO grade II and III tumors are heterogeneous and, in some cases, can develop from a prior lower grade meningioma, although most arise de novo. Mechanisms leading to progression or implicated in de novo grade II and III tumorigenesis are poorly understood. ...[more]

PMID: 31039818

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Project description:Homozygous CDKN2A/B deletion has been associated with an increased risk of recurrence in meningiomas. However, the evidence is confined to a limited number of studies, and the importance of heterozygous CDKN2A/B deletions remains insufficiently investigated. Hence, the present meta-analysis reconstructs individual patient data (IPD) and reconstructs the probabilities of progression-free survival (PFS) stratified by CDKN2A/B status. IPD of PFS rates were extracted from published Kaplan-Meier plots using the R package IPDfromKM in R studio (RStudio, Boston, MA, USA). Reconstructed Kaplan-Meier Plots of the pooled IPD data were created. One-stage and two-stage meta-analyses were performed. Hazard ratios (HR) were used as effective measures. Of 181 records screened, four articles with 2521 participants were included. The prevalence of homozygous CDKN2A/B deletions in the included studies was 0.049 (95% CI 0.040-0.057), with higher tumor grades associated with a significantly greater proportion of CDKN2A/B deletions. The reconstructed PFS curves for the pooled cohort showed that the median PFS time of patients with a CDKN2A/B wild-type status, heterozygous or homozygous CDKN2A/B deletion was 180.0 (95% CI 145.7-214.3), 26.1 (95% CI 23.3-29.0), and 11.00 (95% CI 8.6-13.3) months, respectively (p < 0.0001). Both hetero- or homozygous CDKN2A/B deletions were significantly associated with shortened time to meningioma progression. One-stage meta-analysis showed that hetero- (HR: 5.5, 95% CI 4.0-7.6, p < 0.00001) and homozygous CDKN2A/B deletions (HR: 8.4, 95% CI 6.4-11.0, p < 0.00001) are significantly associated with shortened time to meningioma progression. Multivariable Cox regression analysis of progression in a subgroup with available covariates (age, sex, WHO grade, and TERT status) and also two-stage meta-analysis confirmed and validated the results of the one-stage analysis that both heterozygous and homozygous CDKN2A/B deletions are of prognostic importance. Further large-scale studies of WHO grade 2 and 3 meningiomas are needed to validate the importance of heterozygous CDKN2A/B deletions with consideration of established factors.

Dataset Information

Transcriptome signatures associated with meningioma progression.

Publications

Transcriptome signatures associated with meningioma progression.

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