Universität zu Köln

Juenger, Stephanie T., Andreiuolo, Felipe, Mynarek, Martin, Doerner, Evelyn, zur Muehlen, Anja, Rutkowski, Stefan, von Bueren, Andre O. and Pietsch, Torsten ORCID: 0000-0003-0763-6506 (2020). Ependymomas in infancy: underlying genetic alterations, histological features, and clinical outcome. Childs Nerv. Syst., 36 (11). S. 2693 - 2701. NEW YORK: SPRINGER. ISSN 1433-0350

Full text not available from this repository.

Abstract

Introduction Young age is an adverse prognostic factor in children with ependymomas. Treatment of these infants is challenging since beneficial therapeutic options are limited. As ependymomas are considered a biologically heterogeneous group, we aimed to characterize infant ependymomas with regard to their histological and genetic features. Materials and methods We analyzed 28 ependymomas occurring in children younger than 18 months at diagnosis enrolled into the HIT2000-E protocols with the aim to postpone irradiation until the age of 18 months if possible. All cases underwent neuropathological review, including immunohistochemical characterization. Genome-wide copy number alterations (CNA) were assessed by molecular inversion probe assays, and RELA and YAP1 fusions were detected by RT-PCR and sequencing. Results All infant ependymomas were anaplastic (WHO grade III). Twenty-one (75%) cases were located in the posterior fossa. Gross total resection was accomplished in 12 (57%) of these cases. All posterior fossa tumors showed loss of H3-K27me(3) characteristic of PFA ependymomas. CNA analysis showed a stable genome in all cases with lack of chromosome 1q gain, an adverse prognostic marker in PFA ependymomas of older children. However, after a median follow-up of 5.4 years, 15 (71%) relapsed, and 9 (43%) died. Seven ependymomas (25%) occurred in the supratentorial region. Gross total resection could be achieved in only two of these cases. Four tumors carried C11orf95-RELA fusions, and two cases had typical YAP1-MAMLD1 fusions (one case was not analyzable). The RELA-fused cases did not display CDKN2A loss as an adverse indicator of prognosis in this disease entity. Although three infants (43%) with supratentorial ependymomas relapsed, all patients survived (median follow-up, 8.0 years). Conclusion Infant ependymomas seem to fall into three biological entities, with supratentorial tumors carrying RELA or YAP fusions and PFA posterior fossa ependymomas. The latter showed a poor outcome even though chromosome 1q gain was absent.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Juenger, Stephanie T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Andreiuolo, Felipe UNSPECIFIED UNSPECIFIED UNSPECIFIED Mynarek, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Doerner, Evelyn UNSPECIFIED UNSPECIFIED UNSPECIFIED zur Muehlen, Anja UNSPECIFIED UNSPECIFIED UNSPECIFIED Rutkowski, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED von Bueren, Andre O. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pietsch, Torsten UNSPECIFIED orcid.org/0000-0003-0763-6506 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-332562
DOI:	10.1007/s00381-020-04655-x
Journal or Publication Title:	Childs Nerv. Syst.
Volume:	36
Number:	11
Page Range:	S. 2693 - 2701
Date:	2020
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1433-0350
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PEDIATRIC INTRACRANIAL EPENDYMOMAS; POSTERIOR-FOSSA EPENDYMOMA; PATHOLOGICAL ACTIVATION; CHILDREN; IRRADIATION; SOCIETY; TUMORS; TRIAL; AGE Multiple languages Clinical Neurology; Pediatrics; Surgery Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/33256