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Transcriptional profiling of paediatric ependymomas identifies prognostically significant groups.

ABSTRACT: 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.

SUBMITTER: Lastowska M

PROVIDER: S-EPMC8503892 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Transcriptional profiling of paediatric ependymomas identifies prognostically significant groups.

Łastowska Maria M Matyja Ewa E Sobocińska Anna A Wojtaś Bartosz B Niemira Magdalena M Szałkowska Anna A Krętowski Adam A Karkucińska-Więckowska Agnieszka A Kaleta Magdalena M Ejmont Maria M Tarasińska Magdalena M Perek-Polnik Marta M Dembowska-Bagińska Bożenna B Pronicki Maciej M Grajkowska Wiesława W Trubicka Joanna J

The journal of pathology. Clinical research 20210727 6

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. ...[more]

PMID: 34314101

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Transcriptional profiling of paediatric ependymomas identifies prognostically significant groups.

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Transcriptional profiling of paediatric ependymomas identifies prognostically significant groups.

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