Dimorphic glioblastoma with glial and epithelioid phenotypes: Clonal evolution and immune selection
PurposeEpithelioid glioblastoma is an unusual histologic variant of malignant glioma. The present study investigates both the genomic and transcriptomic determinants that may promote the development of this tumor.MethodsWhole-exome sequencing (WES) and whole-transcriptome sequencing (WTS) were perfo...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Neurology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2022.1017087/full |
| _version_ | 1797956463950299136 |
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| author | Mark Willy L. Mondia Michael A. Kritselis John E. Donahue Heinrich Elinzano Sasmit Sarangi David Bryant Marzia Capelletti W. Michael Korn Esther Yu Sherry Yan Steven A. Toms Eric T. Wong Eric T. Wong Eric T. Wong Eric T. Wong |
| author_facet | Mark Willy L. Mondia Michael A. Kritselis John E. Donahue Heinrich Elinzano Sasmit Sarangi David Bryant Marzia Capelletti W. Michael Korn Esther Yu Sherry Yan Steven A. Toms Eric T. Wong Eric T. Wong Eric T. Wong Eric T. Wong |
| author_sort | Mark Willy L. Mondia |
| collection | DOAJ |
| description | PurposeEpithelioid glioblastoma is an unusual histologic variant of malignant glioma. The present study investigates both the genomic and transcriptomic determinants that may promote the development of this tumor.MethodsWhole-exome sequencing (WES) and whole-transcriptome sequencing (WTS) were performed on an epithelioid glioblastoma, along with a specific bioinformatic pipeline to generate electronic karyotyping and investigate the tumor immune microenvironment. Microdissected sections containing typical glioblastoma features and epithelioid morphology were analyzed separately using the same methodologies.ResultsAn epithelioid glioblastoma, with immunopositivity for GFAP, Olig-2, and ATRX but negative for IDH-1 and p53, was identified. The tumor cell content from microdissection was estimated to be 85–90% for both histologic tumor components. WES revealed that both glioma and epithelioid sections contained identical point mutations in PTEN, RB1, TERT promoter, and TP53. Electronic karyotype analysis also revealed similar chromosomal copy number alterations, but the epithelioid component showed additional abnormalities that were not found in the glioblastoma component. The tumor immune microenvironments were strikingly different and WTS revealed high levels of transcripts from myeloid cells as well as M1 and M2 macrophages in the glioma section, while transcripts from CD4+ lymphocytes and NK cells predominated in the epithelioid section.ConclusionEpithelioid glioblastoma may be genomically more unstable and oncogenically more advanced, harboring an increased number of mutations and karyotype abnormalities, compared to typical glioblastomas. The tumor immune microenvironment is also different. |
| first_indexed | 2024-04-10T23:49:41Z |
| format | Article |
| id | doaj.art-e652121a3ac1494f83333864a668e459 |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-04-10T23:49:41Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-e652121a3ac1494f83333864a668e4592023-01-10T20:47:42ZengFrontiers Media S.A.Frontiers in Neurology1664-22952023-01-011310.3389/fneur.2022.10170871017087Dimorphic glioblastoma with glial and epithelioid phenotypes: Clonal evolution and immune selectionMark Willy L. Mondia0Michael A. Kritselis1John E. Donahue2Heinrich Elinzano3Sasmit Sarangi4David Bryant5Marzia Capelletti6W. Michael Korn7Esther Yu8Sherry Yan9Steven A. Toms10Eric T. Wong11Eric T. Wong12Eric T. Wong13Eric T. Wong14Department of Neurosciences, College of Medicine and Philippine General Hospital, University of the Philippines Manila, Manila, PhilippinesDepartment of Pathology and Laboratory Medicine, The Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI, United StatesDepartment of Pathology and Laboratory Medicine, The Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI, United StatesDepartment of Neurology, The Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI, United StatesDepartment of Neurology, The Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI, United StatesCaris Life Sciences, Irving, TX, United StatesCaris Life Sciences, Irving, TX, United StatesCaris Life Sciences, Irving, TX, United StatesDepartment of Radiation Oncology, The Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI, United StatesDepartment of Radiation Oncology, The Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI, United StatesDepartment of Neurosurgery, The Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI, United StatesDepartment of Neurology, The Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI, United StatesDepartment of Radiation Oncology, The Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI, United StatesDepartment of Neurosurgery, The Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI, United StatesDivision of Hematology/Oncology, Department of Medicine, The Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI, United StatesPurposeEpithelioid glioblastoma is an unusual histologic variant of malignant glioma. The present study investigates both the genomic and transcriptomic determinants that may promote the development of this tumor.MethodsWhole-exome sequencing (WES) and whole-transcriptome sequencing (WTS) were performed on an epithelioid glioblastoma, along with a specific bioinformatic pipeline to generate electronic karyotyping and investigate the tumor immune microenvironment. Microdissected sections containing typical glioblastoma features and epithelioid morphology were analyzed separately using the same methodologies.ResultsAn epithelioid glioblastoma, with immunopositivity for GFAP, Olig-2, and ATRX but negative for IDH-1 and p53, was identified. The tumor cell content from microdissection was estimated to be 85–90% for both histologic tumor components. WES revealed that both glioma and epithelioid sections contained identical point mutations in PTEN, RB1, TERT promoter, and TP53. Electronic karyotype analysis also revealed similar chromosomal copy number alterations, but the epithelioid component showed additional abnormalities that were not found in the glioblastoma component. The tumor immune microenvironments were strikingly different and WTS revealed high levels of transcripts from myeloid cells as well as M1 and M2 macrophages in the glioma section, while transcripts from CD4+ lymphocytes and NK cells predominated in the epithelioid section.ConclusionEpithelioid glioblastoma may be genomically more unstable and oncogenically more advanced, harboring an increased number of mutations and karyotype abnormalities, compared to typical glioblastomas. The tumor immune microenvironment is also different.https://www.frontiersin.org/articles/10.3389/fneur.2022.1017087/fullepithelioid glioblastomaexome sequencingimmune profiling glioblastoma with glial and epithelioid phenotypesmalignant gliomaclonal evaluation |
| spellingShingle | Mark Willy L. Mondia Michael A. Kritselis John E. Donahue Heinrich Elinzano Sasmit Sarangi David Bryant Marzia Capelletti W. Michael Korn Esther Yu Sherry Yan Steven A. Toms Eric T. Wong Eric T. Wong Eric T. Wong Eric T. Wong Dimorphic glioblastoma with glial and epithelioid phenotypes: Clonal evolution and immune selection Frontiers in Neurology epithelioid glioblastoma exome sequencing immune profiling glioblastoma with glial and epithelioid phenotypes malignant glioma clonal evaluation |
| title | Dimorphic glioblastoma with glial and epithelioid phenotypes: Clonal evolution and immune selection |
| title_full | Dimorphic glioblastoma with glial and epithelioid phenotypes: Clonal evolution and immune selection |
| title_fullStr | Dimorphic glioblastoma with glial and epithelioid phenotypes: Clonal evolution and immune selection |
| title_full_unstemmed | Dimorphic glioblastoma with glial and epithelioid phenotypes: Clonal evolution and immune selection |
| title_short | Dimorphic glioblastoma with glial and epithelioid phenotypes: Clonal evolution and immune selection |
| title_sort | dimorphic glioblastoma with glial and epithelioid phenotypes clonal evolution and immune selection |
| topic | epithelioid glioblastoma exome sequencing immune profiling glioblastoma with glial and epithelioid phenotypes malignant glioma clonal evaluation |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2022.1017087/full |
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