Molecular Profiling Reclassifies Adult Astroblastoma into Known and Clinically Distinct Tumor Entities with Frequent Mitogen-Activated Protein Kinase Pathway Alterations

Media type: E-Article
Title: Molecular Profiling Reclassifies Adult Astroblastoma into Known and Clinically Distinct Tumor Entities with Frequent Mitogen-Activated Protein Kinase Pathway Alterations
Contributor: Boisseau, William; Euskirchen, Philipp; Mokhtari, Karima; Dehais, Caroline; Touat, Mehdi; Hoang-Xuan, Khê; Sanson, Marc; Capelle, Laurent; Nouet, Aurélien; Karachi, Carine; Bielle, Franck; Guégan, Justine; Marie, Yannick; Martin-Duverneuil, Nadine; Taillandier, Luc; Rousseau, Audrey; Delattre, Jean-Yves; Idbaih, Ahmed
imprint: Oxford University Press (OUP), 2019
Published in: The Oncologist
Language: English
DOI: 10.1634/theoncologist.2019-0223
ISSN: 1083-7159; 1549-490X
Keywords: Cancer Research ; Oncology
Origination:
Footnote:
Description: <jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Astroblastoma (ABM) is a rare glial brain tumor. Recurrent meningioma 1 (MN1) alterations have been recently identified in most pediatric cases. Adolescent and adult cases, however, remain molecularly poorly defined.</jats:p></jats:sec><jats:sec><jats:title>Materials and Methods</jats:title><jats:p>We performed clinical and molecular characterization of a retrospective cohort of 14 adult and 1 adolescent ABM.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Strikingly, we found that MN1 fusions are a rare event in this age group (1/15). Using methylation profiling and targeted sequencing, most cases were reclassified as either pleomorphic xanthoastrocytomas (PXA)-like or high-grade glioma (HGG)-like. PXA-like ABM show BRAF mutation (6/7 with V600E mutation and 1/7 with G466E mutation) and CD34 expression. Conversely, HGG-like ABM harbored specific alterations of diffuse midline glioma (2/5) or glioblastoma (GBM; 3/5). These latter patients showed an unfavorable clinical course with significantly shorter overall survival (p = .021). Mitogen-activated protein kinase pathway alterations (including FGFR fusion, BRAF and NF1 mutations) were present in 10 of 15 patients and overrepresented in the HGG-like group (3/5) compared with previously reported prevalence of these alterations in GBM and diffuse midline glioma.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>We suggest that gliomas with astroblastic features include a variety of molecularly sharply defined entities. Adult ABM harboring molecular features of PXA and HGG should be reclassified. Central nervous system high-grade neuroepithelial tumors with MN1 alterations and histology of ABM appear to be uncommon in adults. Astroblastic morphology in adults should thus prompt thorough molecular investigation aiming at a clear histomolecular diagnosis and identifying actionable drug targets, especially in the mitogen-activated protein kinase pathway.</jats:p></jats:sec><jats:sec><jats:title>Implications for Practice</jats:title><jats:p>Astroblastoma (ABM) remains a poorly defined and controversial entity. Although meningioma 1 alterations seem to define a large subset of pediatric cases, adult cases remain molecularly poorly defined. This comprehensive molecular characterization of 1 adolescent and 14 adult ABM revealed that adult ABM histology comprises several molecularly defined entities, which explains clinical diversity and identifies actionable targets. Namely, pleomorphic xanthoastrocytoma-like ABM cases show a favorable prognosis whereas high-grade glioma (glioblastoma and diffuse midline gliome)-like ABM show significantly worse clinical courses. These results call for in-depth molecular analysis of adult gliomas with astroblastic features for diagnostic and therapeutic purposes.</jats:p></jats:sec>
Access State: Open Access

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