Characterization of global 5-hydroxymethylcytosine in pediatric posterior fossa ependymoma

Tao Wu,Peng Li,Fu Zhao,Zhi-Wei Zhang,Zhijun Yang,Wei-Min Tong,Pinan Liu,Chunde Li,Shiwei Li,Bo Wang,Jing Zhang,Yamei Niu

doi:10.1186/s13148-020-0809-8

Abstract

Background5-Hydroxymethylcytosine (5hmC) is a novel epigenetic mark and may be involved in the mechanisms of tumorigenesis and malignant transformation. However, the role of 5hmC in ependymoma, the third most common brain tumor in children, remains unclear. The aim of this study sought to identify the characterization of 5hmC levels in pediatric posterior fossa ependymoma and to evaluate whether 5hmC levels could be a potential factor to predict clinical outcomes.ResultsOur results showed that 5hmC levels were globally decreased in posterior fossa ependymoma compared with normal cerebellum tissues (P < 0.001). Group A posterior fossa ependymomas had higher 5hmC levels than group B tumors (P = 0.007). Moreover, 5hmC levels positively correlated with Ki-67 index in posterior fossa ependymoma (r = 0.428, P = 0.003). Multivariate Cox hazards model revealed that patients with high 5hmC levels (> 0.102%) had worse PFS and OS than patients with lower 5hmC levels (< 0.102%) (PFS: HR = 3.014; 95% CI, 1.040–8.738; P = 0.042; OS: HR = 2.788; 95% CI, 0.974–7.982; P = 0.047).ConclusionsOur findings suggest that loss of 5hmC is an epigenetic hallmark for pediatric posterior fossa ependymoma. 5hmC levels may represent a potential biomarker to predict prognosis in children with posterior fossa ependymoma.

Highlights

Ependymoma (EPN) is a relatively rare neuroepithelial tumor that arises throughout the whole neuraxis [1]
We performed immunostaining of H3K27me3 to distinguish Group A posterior fossa ependymoma (EPN_PFA) from Group B posterior fossa ependymoma (EPN_PFB) (Additional file 1: Figure S1A)
We found that 35 of 45 (77.8%) were negative for H3K27me3 staining and designated as EPN_PFA, while 10 of 45 (22.2%) were positive as PFB (Additional file 1: Figure S1B)

Summary

Introduction

Ependymoma (EPN) is a relatively rare neuroepithelial tumor that arises throughout the whole neuraxis [1]. Intracranial EPN predominantly occurs in children and adolescents, with two third of those tumors located in posterior fossa [1, 2]. CpGi hypermethylation with 1q gain and occurs predominantly in infancy and young children These subgroup tumors exhibit global low H3K27me3 [7,8,9], global DNA hypomethylation [7], and high expression of EZHIP [10]. Group B ependymoma (EPN_PFB) presents with CpGi hypomethylation and primarily occurs in adolescences and young adults. EPN_PFA tumors are often difficult to completely resect and bear a dismal prognosis, while EPN_PFB tumors are less invasive and carry a favorable prognosis [4, 5] It suggests that epigenetic mechanisms play an essential role in EPN_PF pathogenesis and tumor maintenance

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