Supratentorial ependymomas of childhood carry C11orf95–RELA fusions leading to pathological activation of the NF-κB signaling pathway

Pietsch, Torsten; Wohlers, Inken; Goschzik, Tobias; Dreschmann, Verena; Denkhaus, Dorota; Dörner, Evelyn; Rahmann, Sven; Klein-Hitpaß, Ludger

doi:10.1007/s00401-014-1264-4

Cited by 116 publications

(100 citation statements)

References 7 publications

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“…30 RFPE is characterized by a RELA fusion, most commonly the C11orf95-RELA (~70%), by supratentorial location, usually affecting children, and less commonly, adults. 32,33 According to a single study, RFPEs have a worse prognosis compared to other supratentorial molecular groups (see below). 34 This entity is morphologically diverse and can be either classic or anaplastic (WHO grade II or III).…”

Section: Pathologymentioning

confidence: 99%

Case-based review: ependymomas in adults

Cachia

Johnson

Kaufmann

et al. 2018

Neuro-Oncology Practice

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Ependymomas are rare primary central nervous system (CNS) tumors in adults. They occur most commonly in the spinal cord, and have classically been graded histologically into World Health Organization (WHO) grades I, II, or III based on the level of anaplasia. Recent data are showing that genetic heterogeneity occurs within the same histological subgroup and that ependymomas arising from different CNS locations have different molecular signatures. This has renewed interest in developing targeting therapies based on molecular profiles especially given the variable outcomes with radiation and the poor results with cytotoxic agents. In this paper, we present the case of a 46-year-old woman with a classic presentation of spinal cord ependymoma and discuss the current histopathological and molecular classification for ependymomas as well as current guidelines for patient management.

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Section: Pathologymentioning

confidence: 99%

Case-based review: ependymomas in adults

Cachia

Johnson

Kaufmann

et al. 2018

Neuro-Oncology Practice

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“…Furthermore, recently two distinct molecular ependymoma subgroups could be defined in the infra- and supratentorial compartment, respectively [27, 28]. The two supratentorial subgroups are characterized by fusions of the RELA or YAP1 gene, respectively [27, 29, 30] and patients with RELA fusion were shown to have a worse prognosis in one study [27]. Posterior fossa tumors could be classified into Group A (EPN-PF-A) and B (EPN-PF-B) tumors [27, 28].…”

Section: Introductionmentioning

confidence: 99%

Chromosome 1q gain and tenascin-C expression are candidate markers to define different risk groups in pediatric posterior fossa ependymoma

Araki

Chocholous

Gojo

et al. 2016

acta neuropathol commun

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Intracranial classic (WHO grade II) and anaplastic (WHO grade III) ependymomas are among the most common tumors in pediatric patients and have due to frequent recurrences and late relapses a relatively poor outcome. The impact of histopathological grading on patient outcome is controversial and therefore, molecular prognostic and predictive markers are needed to improve patient outcome. To date, the most promising candidate marker is chromosome 1q gain, which has been associated in independent studies with adverse outcome. Furthermore, gene expression and methylation profiles revealed distinct molecular subgroups in the supratentorial and posterior fossa (PF) compartment and Laminin alpha-2 (LAMA2) and Neural Epidermal Growth Factor Like-2 (NELL2) were suggested as surrogate markers for the two PF subgroups PF-EPN-A and PF-EPN-B. PF-EPN-A tumors were also characterized by tenascin-C (TNC) expression and tenascin-C has been suggested as candidate gene on 9q, involved in tumor progression. Therefore, we have analyzed the status of chromosome 1q, TNC, LAMA2, and NELL2 expression in a series of pediatric PF ependymomas in terms of their frequency, associations among themselves, and clinical parameters, as well as their prognostic impact. We confirm the negative prognostic impact of 1q gain and TNC expression and could classify PF ependymomas by these two markers into three molecular subgroups. Tumors with combined 1q gain and TNC expression had the poorest, tumors without 1q gain and TNC expression had a favorable and TNC positive 1q non-gained cases had an intermediate outcome. We found also differences in age and tumor grade in the three subgroups and thus, provide evidence that PF pediatric ependymomas can be divided by chromosome 1q status and TNC expression in three molecular subgroups with distinct clinico-pathological features. These analyses require only few amounts of tumor tissue, are broadly available in the routine clinical neuropathological setting and thus, could be used in further therapy trials to optimize treatment of ependymoma patients.

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“…The pathologic findings for AEs establish more aggressive tumor subtypes that complemented with genetic and biomolecular studies (review more relevant markers in the review section) amplify the information that allows to better define the factors of prognostic type, to individualize treatments, in the sample of patients it was not possible to typify the markers to establish their relation with clinical pathological findings [2,4,9].…”

Section: Discussionmentioning

confidence: 99%

“…They are related in several studies with variable results. Currently the alteration in chromosome 11q.13 generated interest, there is a fusion protein called C11ORF95-RELA that enters the cell nucleus activating genes related to the NF-KB pathway (nuclear factor kapa beta) generating changes in neural stem cells precursors of ependymal cells; was more reported in supratentorial ependymomas [3][4][5].…”

Section: Reviewmentioning

confidence: 99%

Anaplastic Ependymomas, Report of 3 Pediatric Cases. Update on Molecular Markers - Risk Groups and Therapeutic Options

Cafiero¹

2017

JCPCR

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Supratentorial ependymomas of childhood carry C11orf95–RELA fusions leading to pathological activation of the NF-κB signaling pathway

Cited by 116 publications

References 7 publications

Case-based review: ependymomas in adults

Case-based review: ependymomas in adults

Chromosome 1q gain and tenascin-C expression are candidate markers to define different risk groups in pediatric posterior fossa ependymoma

Anaplastic Ependymomas, Report of 3 Pediatric Cases. Update on Molecular Markers - Risk Groups and Therapeutic Options

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