EZH2 inhibitory protein (EZHIP/Cxorf67) expression correlates strongly with H3K27me3 loss in posterior fossa ependymomas and is mutually exclusive with H3K27M mutations
| Autor: | Aruna Nambirajan, Chitra Sarkar, Vaishali Suri, Mehar Chand Sharma, Madhu Rajeshwari, Meher Tej Boorgula, Ajay Garg, Ramesh Doddamani, Agrima Sharma |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Male Cancer Research Pathology medicine.medical_specialty Jumonji Domain-Containing Histone Demethylases Adolescent Gene Expression Locus (genetics) Inhibitory postsynaptic potential 03 medical and health sciences Young Adult 0302 clinical medicine medicine Humans Prospective Studies Child ATRX Retrospective Studies Oncogene Proteins Membrane Glycoproteins biology Surrogate endpoint Brain Neoplasms EZH2 Tenascin C Infant General Medicine Middle Aged Histone Oncology Ependymoma 030220 oncology & carcinogenesis Child Preschool Mutation biology.protein Immunohistochemistry Female Neurology (clinical) Dura Mater 030217 neurology & neurosurgery |
| Zdroj: | Brain tumor pathology. 38(1) |
| ISSN: | 1861-387X |
| Popis: | The PFA molecular subgroup of posterior fossa ependymomas (PF-EPNs) shows poor outcome. H3K27me3 (me3) loss by immunohistochemistry (IHC) is a surrogate marker for PFA wherein its loss is attributed to overexpression of Cxorf67/EZH2 inhibitory protein (EZHIP), C17orf96, and ATRX loss. We aimed to subgroup PF-EPNs using me3 IHC and study correlations of the molecular subgroups with other histone related proteins, 1q gain, Tenascin C and outcome. IHC for me3, acetyl-H3K27, H3K27M, ATRX, EZH2, EZHIP, C17orf96, Tenascin-C, and fluorescence in-situ hybridisation for chromosome 1q25 locus were performed on an ambispective PF-EPN cohort (2003–2019). H3K27M-mutant gliomas were included for comparison. Among 69 patients, PFA (me3 loss) constituted 64%. EZHIP overexpression and 1q gain were exclusive to PFA seen in 72% and 19%, respectively. Tenascin C was more frequently positive in PFA (p = 0.02). H3K27M expression and ATRX loss were noted in one case of PFA–EPN each. All H3K27M-mutant gliomas (n = 8) and PFA-EPN (n = 1) were EZHIP negative. C17orf96 and acetyl-H3K27 expression did not correlate with me3 loss. H3K27me3 is a robust surrogate for PF-EPN molecular subgrouping. EZHIP overexpression was exclusive to PFA EPNs and was characteristically absent in midline gliomas and the rare PFA harbouring H3K27M mutations representing mutually exclusive pathways leading to me3 loss. |
| Databáze: | OpenAIRE |
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