e-Article
Transcriptional profiling of paediatric ependymomas identifies prognostically significant groups
Document Type
Report
Author
Łastowska, Maria; Matyja, Ewa; Sobocińska, Anna; Wojtaś, Bartosz; Niemira, Magdalena; Szałkowska, Anna; Krętowski, Adam; Karkucińska‐Więckowska, Agnieszka; Kaleta, Magdalena; Ejmont, Maria; Tarasińska, Magdalena; Perek‐Polnik, Marta; Dembowska‐Bagińska, Bożenna; Pronicki, Maciej; Grajkowska, Wiesława; Trubicka, Joanna
Source
The Journal of Pathology: Clinical Research. November 2021, Vol. 7 Issue 6, p565, 12 p.
Subject
Language
English
Abstract
Introduction The integrated use of whole‐genome analysis technologies has revealed the site‐specific molecular heterogeneity of ependymomas. The majority of supratentorial tumours contain oncogenic fusions between the genes C11orf95 and RELA [...]
: The majority of supratentorial ependymomas in children contain oncogenic fusions, such as ZFTA–RELA or YAP1‐MAMLD1. In contrast, posterior fossa (PF) ependymomas lack recurrent somatic mutations and are classified based on gene expression or methylation profiling into group A (PFA) and group B (PFB). We have applied a novel method, NanoString nCounter Technology, to identify four molecular groups among 16 supratentorial and 50 PF paediatric ependymomas, using 4–5 group‐specific signature genes. Clustering analysis of 16 supratentorial ependymomas revealed 9 tumours with a RELA fusion‐positive signature (RELA+), 1 tumour with a YAP1 fusion‐positive signature (YAP1+), and 6 not‐classified tumours. Additionally, we identified one RELA+ tumour among historically diagnosed CNS primitive neuroectodermal tumour samples. Overall, 9 of 10 tumours with the RELA+ signature possessed the ZFTA‐RELA fusion as detected by next‐generation sequencing (p = 0.005). Similarly, the only tumour with a YAP1+ signature exhibited the YAP1‐MAMLD1 fusion. Among the remaining unclassified ependymomas, which did not exhibit the ZFTA‐RELA fusion, the ZFTA‐MAML2 fusion was detected in one case. Notably, among nine ependymoma patients with the RELA+ signature, eight survived at least 5 years after diagnosis. Clustering analysis of PF tumours revealed 42 samples with PFA signatures and 7 samples with PFB signatures. Clinical characteristics of patients with PFA and PFB ependymomas corroborated the previous findings. In conclusion, we confirm here that the NanoString method is a useful single tool for the diagnosis of all four main molecular groups of ependymoma. The differences in reported survival rates warrant further clinical investigation of patients with the ZFTA‐RELA fusion.
: The majority of supratentorial ependymomas in children contain oncogenic fusions, such as ZFTA–RELA or YAP1‐MAMLD1. In contrast, posterior fossa (PF) ependymomas lack recurrent somatic mutations and are classified based on gene expression or methylation profiling into group A (PFA) and group B (PFB). We have applied a novel method, NanoString nCounter Technology, to identify four molecular groups among 16 supratentorial and 50 PF paediatric ependymomas, using 4–5 group‐specific signature genes. Clustering analysis of 16 supratentorial ependymomas revealed 9 tumours with a RELA fusion‐positive signature (RELA+), 1 tumour with a YAP1 fusion‐positive signature (YAP1+), and 6 not‐classified tumours. Additionally, we identified one RELA+ tumour among historically diagnosed CNS primitive neuroectodermal tumour samples. Overall, 9 of 10 tumours with the RELA+ signature possessed the ZFTA‐RELA fusion as detected by next‐generation sequencing (p = 0.005). Similarly, the only tumour with a YAP1+ signature exhibited the YAP1‐MAMLD1 fusion. Among the remaining unclassified ependymomas, which did not exhibit the ZFTA‐RELA fusion, the ZFTA‐MAML2 fusion was detected in one case. Notably, among nine ependymoma patients with the RELA+ signature, eight survived at least 5 years after diagnosis. Clustering analysis of PF tumours revealed 42 samples with PFA signatures and 7 samples with PFB signatures. Clinical characteristics of patients with PFA and PFB ependymomas corroborated the previous findings. In conclusion, we confirm here that the NanoString method is a useful single tool for the diagnosis of all four main molecular groups of ependymoma. The differences in reported survival rates warrant further clinical investigation of patients with the ZFTA‐RELA fusion.