Epigenetic and genomic profiling of chordoid meningioma: implications for clinical management
Abstract Chordoid meningioma is a morphological variant of meningioma designated as WHO grade 2. However, the recurrence rates varied widely in different case series, and to date, a unifying molecular genetic signature has not been identified. Among 1897 meningiomas resected at our institution, we i...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-04-01
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| Series: | Acta Neuropathologica Communications |
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| Online Access: | https://doi.org/10.1186/s40478-022-01362-3 |
| _version_ | 1818060634353303552 |
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| author | Elena V. Daoud Kelsey Zhu Bruce Mickey Hussein Mohamed Mandisa Wen Michael Delorenzo Ivy Tran Jonathan Serrano Kimmo J. Hatanpaa Jack M. Raisanen Matija Snuderl Chunyu Cai |
| author_facet | Elena V. Daoud Kelsey Zhu Bruce Mickey Hussein Mohamed Mandisa Wen Michael Delorenzo Ivy Tran Jonathan Serrano Kimmo J. Hatanpaa Jack M. Raisanen Matija Snuderl Chunyu Cai |
| author_sort | Elena V. Daoud |
| collection | DOAJ |
| description | Abstract Chordoid meningioma is a morphological variant of meningioma designated as WHO grade 2. However, the recurrence rates varied widely in different case series, and to date, a unifying molecular genetic signature has not been identified. Among 1897 meningiomas resected at our institution, we identified 12 primary chordoid meningiomas from 12 patients. Histologically, all 12 cases had predominant (> 50%) chordoid morphology. Ten were otherwise grade 1, and two were also atypical. We performed DNA global methylation profile, copy number variation analysis, and targeted next-generation sequencing on 11 chordoid meningiomas, and compared to those of 51 non-chordoid, mostly high grade meningiomas. The chordoid meningiomas demonstrated a unique methylation profile in tSNE, UMAP, and hierarchical heatmap clustering analyses of the most differentially methylated CpGs. The most common copy number variation in chordoid meningioma was loss of 1p (7/11, 64%). Three chordoid meningiomas had 2p loss, which was significantly higher than the non-chordoid control cohort (27% vs 7.2%, p = 0.035). 22q loss was only seen in the two cases with additional atypical histological features. Chordoid meningiomas were enriched in mutations in chromatin remodeling genes EP400 (8/11,73%) KMT2C (4/11, 36%) and KMT2D (4/11, 36%), and showed low or absent NF2, TERT, SMO, and AKT1 mutations. Prognosis wise, only one case recurred. This case had atypical histology and high-grade molecular features including truncating NF2 mutation, 1p, 8p, 10, 14, 22q loss, and homozygous deletion of CDKN2A/B. Progression free survival of chordoid, otherwise grade 1 meningioma was comparable to non-chordoid WHO grade 1 meningioma (p = 0.75), and significantly better than chordoid WHO grade 2 meningioma (p = 0.019). Conclusion: the chordoid histology alone may not justify a universal WHO grade 2 designation. Screening for additional atypical histological or molecular genetic features is recommended. |
| first_indexed | 2024-12-10T13:35:32Z |
| format | Article |
| id | doaj.art-13cb9aba473648c1bc9705a74565ba16 |
| institution | Directory Open Access Journal |
| issn | 2051-5960 |
| language | English |
| last_indexed | 2024-12-10T13:35:32Z |
| publishDate | 2022-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj.art-13cb9aba473648c1bc9705a74565ba162022-12-22T01:46:50ZengBMCActa Neuropathologica Communications2051-59602022-04-0110111210.1186/s40478-022-01362-3Epigenetic and genomic profiling of chordoid meningioma: implications for clinical managementElena V. Daoud0Kelsey Zhu1Bruce Mickey2Hussein Mohamed3Mandisa Wen4Michael Delorenzo5Ivy Tran6Jonathan Serrano7Kimmo J. Hatanpaa8Jack M. Raisanen9Matija Snuderl10Chunyu Cai11Department of Pathology, UT Southwestern Medical CenterDepartment of Pathology, NYU Langone Medical CenterDepartment of Neurological Surgery, UT Southwestern Medical CenterDepartment of Pathology, NYU Langone Medical CenterDepartment of Pathology, NYU Langone Medical CenterDepartment of Pathology, NYU Langone Medical CenterDepartment of Pathology, NYU Langone Medical CenterDepartment of Pathology, NYU Langone Medical CenterDepartment of Pathology, UT Southwestern Medical CenterDepartment of Pathology, UT Southwestern Medical CenterDepartment of Pathology, NYU Langone Medical CenterDepartment of Pathology, UT Southwestern Medical CenterAbstract Chordoid meningioma is a morphological variant of meningioma designated as WHO grade 2. However, the recurrence rates varied widely in different case series, and to date, a unifying molecular genetic signature has not been identified. Among 1897 meningiomas resected at our institution, we identified 12 primary chordoid meningiomas from 12 patients. Histologically, all 12 cases had predominant (> 50%) chordoid morphology. Ten were otherwise grade 1, and two were also atypical. We performed DNA global methylation profile, copy number variation analysis, and targeted next-generation sequencing on 11 chordoid meningiomas, and compared to those of 51 non-chordoid, mostly high grade meningiomas. The chordoid meningiomas demonstrated a unique methylation profile in tSNE, UMAP, and hierarchical heatmap clustering analyses of the most differentially methylated CpGs. The most common copy number variation in chordoid meningioma was loss of 1p (7/11, 64%). Three chordoid meningiomas had 2p loss, which was significantly higher than the non-chordoid control cohort (27% vs 7.2%, p = 0.035). 22q loss was only seen in the two cases with additional atypical histological features. Chordoid meningiomas were enriched in mutations in chromatin remodeling genes EP400 (8/11,73%) KMT2C (4/11, 36%) and KMT2D (4/11, 36%), and showed low or absent NF2, TERT, SMO, and AKT1 mutations. Prognosis wise, only one case recurred. This case had atypical histology and high-grade molecular features including truncating NF2 mutation, 1p, 8p, 10, 14, 22q loss, and homozygous deletion of CDKN2A/B. Progression free survival of chordoid, otherwise grade 1 meningioma was comparable to non-chordoid WHO grade 1 meningioma (p = 0.75), and significantly better than chordoid WHO grade 2 meningioma (p = 0.019). Conclusion: the chordoid histology alone may not justify a universal WHO grade 2 designation. Screening for additional atypical histological or molecular genetic features is recommended.https://doi.org/10.1186/s40478-022-01362-3Chordoid meningiomaGlobal methylation profileWHO gradePrognosisAtypical meningiomaBrain tumor |
| spellingShingle | Elena V. Daoud Kelsey Zhu Bruce Mickey Hussein Mohamed Mandisa Wen Michael Delorenzo Ivy Tran Jonathan Serrano Kimmo J. Hatanpaa Jack M. Raisanen Matija Snuderl Chunyu Cai Epigenetic and genomic profiling of chordoid meningioma: implications for clinical management Acta Neuropathologica Communications Chordoid meningioma Global methylation profile WHO grade Prognosis Atypical meningioma Brain tumor |
| title | Epigenetic and genomic profiling of chordoid meningioma: implications for clinical management |
| title_full | Epigenetic and genomic profiling of chordoid meningioma: implications for clinical management |
| title_fullStr | Epigenetic and genomic profiling of chordoid meningioma: implications for clinical management |
| title_full_unstemmed | Epigenetic and genomic profiling of chordoid meningioma: implications for clinical management |
| title_short | Epigenetic and genomic profiling of chordoid meningioma: implications for clinical management |
| title_sort | epigenetic and genomic profiling of chordoid meningioma implications for clinical management |
| topic | Chordoid meningioma Global methylation profile WHO grade Prognosis Atypical meningioma Brain tumor |
| url | https://doi.org/10.1186/s40478-022-01362-3 |
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