BCAS1 defines a heterogeneous cell population in diffuse gliomas

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// Raquel Morales-Gallel 1 , * , María José Ulloa-Navas 2 , * , Patricia García-Tárraga 1 , Ricardo Prat-Acín 3 , Gaspar Reynés 4 , Pedro Pérez-Borredá 3 , Luis Rubio 5 , Vivian Capilla-González 6 , Jaime Ferrer-Lozano 5 and José Manuel García-Verdugo 1 1 Laboratory of Comparative Neurobiology, Institute Cavanilles of Biodiversity and Evolutionary Biology, University of Valencia-CIBERNED, Valencia, Spain 2 Department of Neurosurgery, Mayo Clinic, Jacksonville, FL 32224, USA 3 Department of Neurosurgery, Hospital Universitari i Politècnic La Fe, Valencia, Spain 4 Group of Clinical and Translational Research in Cancer, Health Research Institute Hospital Universitari i Politècnic La Fe, Valencia, Spain 5 Department of Pathology, Hospital Universitari i Politècnic La Fe, Valencia, Spain 6 Department of Integrative Pathophysiology and Therapies, Andalusian Center for Molecular Biology and Regenerative Medicine-CABIMER, Junta de Andalucía-University of Pablo de Olavide-University of Seville-CSIC, Seville, Spain * These authors contributed equally to this work Correspondence to: José Manuel García-Verdugo, email: j.manuel.garcia@uv.es Keywords: brain tumor; diffuse glioma; oligodendroglioma; glioblastoma; BCAS1 Received: September 11, 2023 Accepted: December 18, 2023 Published: January 24, 2024 Copyright: © 2024 Morales-Gallel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Oligodendrocyte precursor markers have become of great interest to identify new diagnostic and therapeutic targets for diffuse gliomas, since state-of-the-art studies point towards immature oligodendrocytes as a possible source of gliomagenesis. Brain enriched myelin associated protein 1 (BCAS1) is a novel marker of immature oligodendrocytes and was proposed to contribute to tumorigenesis in non-central nervous system tumors. However, BCAS1 role in diffuse glioma is still underexplored. This study analyzes the expression of BCAS1 in different tumor samples from patients with diffuse gliomas (17 oligodendrogliomas; 8 astrocytomas; 60 glioblastomas) and uncovers the molecular and ultrastructural features of BCAS1 + cells by immunostaining and electron microscopy. Our results show that BCAS1 + cells exhibit stellate or spherical morphology with similar ultrastructural features. Stellate and spherical cells were detected as isolated cells in all studied gliomas. Nevertheless, only stellate cells were found to be proliferative and formed tightly packed nodules with a highly proliferative rate in oligodendrogliomas. Our findings provide a comprehensive characterization of the BCAS1 + cell population within diffuse gliomas. The observed proliferative capacity and distribution of BCAS1 + stellate cells, particularly in oligodendrogliomas, highlight BCAS1 as an interesting marker, warranting further investigation into its role in tumor malignancy.

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