Genomic analysis demonstrates that histologically-defined astroblastomas are molecularly heterogeneous and that tumors with MN1 rearrangement exhibit the most favorable prognosis
Abstract Astroblastoma (AB) is a rare CNS tumor demonstrating abundant astroblastomatous pseudorosettes. Its molecular features have not been comprehensively studied and its status as a tumor entity is controversial. We analyzed a cohort of 27 histologically-defined ABs using DNA methylation profili...
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doaj-efefe643d23d4e53b9215d6a24653c302020-11-25T03:32:28ZengBMCActa Neuropathologica Communications2051-59602019-03-017111110.1186/s40478-019-0689-3Genomic analysis demonstrates that histologically-defined astroblastomas are molecularly heterogeneous and that tumors with MN1 rearrangement exhibit the most favorable prognosisNorman L. Lehman0Aisulu Usubalieva1Tong Lin2Sariah J. Allen3Quynh T. Tran4Bret C. Mobley5Roger E. McLendon6Matthew J. Schniederjan7Maria-Magdalena Georgescu8Marta Couce9Mohanpal S. Dulai10Jack M. Raisanen11Mousa Al Abbadi12Cheryl A. Palmer13Eyas M. Hattab14Brent A. Orr15Department of Pathology and Laboratory Medicine, University of LouisvilleDepartment of Biomedical Informatics, University of Arkansas for Medical SciencesDepartment of Biostatistics, St. Jude Children’s Research HospitalDepartment of Pathology, St. Jude Children’s Research HospitalDepartment of Pathology, St. Jude Children’s Research HospitalDepartment of Pathology, Vanderbilt University School of MedicineDepartments of Pathology, Duke University Medical CenterDepartment of Pathology, Emory UniversityDepartment of Pathology, Louisiana State University Health ShreveportDepartment of Pathology, Case Western Reserve UniversityDepartment of Pathology, Beaumont HospitalDepartment of Pathology, The University of Texas SouthwesternDepartment of Pathology, Microbiology and Forensic Medicine, University of JordanDepartment of Pathology, University of UtahDepartment of Pathology and Laboratory Medicine, University of LouisvilleDepartment of Pathology, St. Jude Children’s Research HospitalAbstract Astroblastoma (AB) is a rare CNS tumor demonstrating abundant astroblastomatous pseudorosettes. Its molecular features have not been comprehensively studied and its status as a tumor entity is controversial. We analyzed a cohort of 27 histologically-defined ABs using DNA methylation profiling, copy number analysis, FISH and site-directed sequencing. Most cases demonstrated mutually exclusive MN1 rearrangements (n = 10) or BRAF V600E mutations (n = 7). Two additional cases harbored RELA rearrangements. Other cases lacked these specific genetic alterations (n = 8). By DNA methylation profiling, tumors with MN1 or RELA rearrangement clustered with high-grade neuroepithelial tumor with MN1 alteration (HGNET-MN1) and RELA-fusion ependymoma, respectively. In contrast, BRAF V600E -mutant tumors grouped with pleomorphic xanthoastrocytoma (PXA). Six additional tumors clustered with either supratentorial pilocytic astrocytoma and ganglioglioma (LGG-PA/GG-ST), normal or reactive cerebrum, or with no defined DNA methylation class. While certain histologic features favored one genetic group over another, no group could be reliably distinguished by histopathology alone. Survival analysis between genetic AB subtypes was limited by sample size, but showed that MN1-rearranged AB tumors were characterized by better overall survival compared to other genetic subtypes, in fact, significantly better than BRAF V600E -mutant tumors (P = 0.013). Our data confirm that histologically-defined ABs are molecularly heterogeneous and do not represent a single entity. They rather encompass several low- to higher-grade glial tumors including neuroepithelial tumors with MN1 rearrangement, PXA-like tumors, RELA ependymomas, and possibly yet uncharacterized lesions. Genetic subtyping of tumors exhibiting AB histology, particularly determination of MN1 and BRAF V600E status, is necessary for important prognostic and possible treatment implications.http://link.springer.com/article/10.1186/s40478-019-0689-3 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Norman L. Lehman Aisulu Usubalieva Tong Lin Sariah J. Allen Quynh T. Tran Bret C. Mobley Roger E. McLendon Matthew J. Schniederjan Maria-Magdalena Georgescu Marta Couce Mohanpal S. Dulai Jack M. Raisanen Mousa Al Abbadi Cheryl A. Palmer Eyas M. Hattab Brent A. Orr |
spellingShingle |
Norman L. Lehman Aisulu Usubalieva Tong Lin Sariah J. Allen Quynh T. Tran Bret C. Mobley Roger E. McLendon Matthew J. Schniederjan Maria-Magdalena Georgescu Marta Couce Mohanpal S. Dulai Jack M. Raisanen Mousa Al Abbadi Cheryl A. Palmer Eyas M. Hattab Brent A. Orr Genomic analysis demonstrates that histologically-defined astroblastomas are molecularly heterogeneous and that tumors with MN1 rearrangement exhibit the most favorable prognosis Acta Neuropathologica Communications |
author_facet |
Norman L. Lehman Aisulu Usubalieva Tong Lin Sariah J. Allen Quynh T. Tran Bret C. Mobley Roger E. McLendon Matthew J. Schniederjan Maria-Magdalena Georgescu Marta Couce Mohanpal S. Dulai Jack M. Raisanen Mousa Al Abbadi Cheryl A. Palmer Eyas M. Hattab Brent A. Orr |
author_sort |
Norman L. Lehman |
title |
Genomic analysis demonstrates that histologically-defined astroblastomas are molecularly heterogeneous and that tumors with MN1 rearrangement exhibit the most favorable prognosis |
title_short |
Genomic analysis demonstrates that histologically-defined astroblastomas are molecularly heterogeneous and that tumors with MN1 rearrangement exhibit the most favorable prognosis |
title_full |
Genomic analysis demonstrates that histologically-defined astroblastomas are molecularly heterogeneous and that tumors with MN1 rearrangement exhibit the most favorable prognosis |
title_fullStr |
Genomic analysis demonstrates that histologically-defined astroblastomas are molecularly heterogeneous and that tumors with MN1 rearrangement exhibit the most favorable prognosis |
title_full_unstemmed |
Genomic analysis demonstrates that histologically-defined astroblastomas are molecularly heterogeneous and that tumors with MN1 rearrangement exhibit the most favorable prognosis |
title_sort |
genomic analysis demonstrates that histologically-defined astroblastomas are molecularly heterogeneous and that tumors with mn1 rearrangement exhibit the most favorable prognosis |
publisher |
BMC |
series |
Acta Neuropathologica Communications |
issn |
2051-5960 |
publishDate |
2019-03-01 |
description |
Abstract Astroblastoma (AB) is a rare CNS tumor demonstrating abundant astroblastomatous pseudorosettes. Its molecular features have not been comprehensively studied and its status as a tumor entity is controversial. We analyzed a cohort of 27 histologically-defined ABs using DNA methylation profiling, copy number analysis, FISH and site-directed sequencing. Most cases demonstrated mutually exclusive MN1 rearrangements (n = 10) or BRAF V600E mutations (n = 7). Two additional cases harbored RELA rearrangements. Other cases lacked these specific genetic alterations (n = 8). By DNA methylation profiling, tumors with MN1 or RELA rearrangement clustered with high-grade neuroepithelial tumor with MN1 alteration (HGNET-MN1) and RELA-fusion ependymoma, respectively. In contrast, BRAF V600E -mutant tumors grouped with pleomorphic xanthoastrocytoma (PXA). Six additional tumors clustered with either supratentorial pilocytic astrocytoma and ganglioglioma (LGG-PA/GG-ST), normal or reactive cerebrum, or with no defined DNA methylation class. While certain histologic features favored one genetic group over another, no group could be reliably distinguished by histopathology alone. Survival analysis between genetic AB subtypes was limited by sample size, but showed that MN1-rearranged AB tumors were characterized by better overall survival compared to other genetic subtypes, in fact, significantly better than BRAF V600E -mutant tumors (P = 0.013). Our data confirm that histologically-defined ABs are molecularly heterogeneous and do not represent a single entity. They rather encompass several low- to higher-grade glial tumors including neuroepithelial tumors with MN1 rearrangement, PXA-like tumors, RELA ependymomas, and possibly yet uncharacterized lesions. Genetic subtyping of tumors exhibiting AB histology, particularly determination of MN1 and BRAF V600E status, is necessary for important prognostic and possible treatment implications. |
url |
http://link.springer.com/article/10.1186/s40478-019-0689-3 |
work_keys_str_mv |
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