The major finding of this report is that primary ciliogenesis is disrupted at an early stage in the majority of human GBM tumors. This finding is important for several reasons. First, these results confirm astrocytoma/glioblastoma cell culture data. Second, it indicates that defects in ciliogenesis are a hallmark of GBM tumor pathology and provides impetus for further study of the relationship between primary cilium defects and other brain tumors such as astrocytoma, oligodendroglioma and medulloblastoma. Third, it provides further evidence that the early stages of ciliogenesis are a critical time in the process of ciliogenesis, thus narrowing the number of target proteins that may underlie these defects. Fourth, it catalogues and describes the key basal body/cilium-related ultrastructural abnormalities that are common between GBM tumors. The ultrastructural description of this study informs which proteins are involved in early ciliogenesis defects and identifies candidates that are currently in the literature. In future, it will be important to elucidate which specific proteins are involved in this critical time period and whether alterations in their expression can restore ciliogenesis and thus restore cell cycle control.
ARM: Antigen retrieval method; CCRK: Cell cycle-related kinase; CSF: Cerebral spinal fluid; DAPI: 4',6-diamidino-2-phenylindole; EM: Electron microscopy; EGFR: Epidermal growth factor receptor; FFPE: Formalin-fixed paraffin embedded; GBM: Glioblastoma multiforme; IIF: Indirect immunofluorescence; IDH: Isocitrate dehydrogenase; MGMT: O6-methylguanine-DNA methyltransferase; PBS: Phosphate buffered saline; PCM: Pericentriolar material; RPE1: Retinal pigment epithelial; Shh: Sonic hedgehog signalling; WHO: World Health Organization.
The authors declare that they have no competing interests.
JJM and JBR obtained the molecular characterization data, carried out the electron microscopy studies, performed indirect immunofluorescence experiments and wrote the first draft of the manuscript. JJM, MJF and JBR conceived of the study design, participated in obtaining ethics approval, interpretation of the data, read, edited and approved the final manuscript. All authors read and approved the final manuscript.
We thank neuropathologists, Drs. Jennifer Chan and Leslie Hamilton, University of Calgary for providing the samples, diagnoses and clinico-pathological information on the tissues obtained from Calgary Laboratory Services. This work was supported in part by the Canadian Institutes for Health Research Grant MOP-57674 (MJF) and the Natural Sciences and Engineering Research Council of Canada Grant 690481 (JBR).
BMC Clin Pathol. 2014;14(40) © 2014 BioMed Central, Ltd.