Pfaff, Elke, El Damaty, Ahmed, Balasubramanian, Gnana Prakash, Blattner-Johnson, Mirjam, Worst, Barbara C., Stark, Sebastian, Witt, Hendrik, Pajtler, Kristian W. ORCID: 0000-0002-3562-6121, van Tilburg, Cornelis M., Witt, Ruth, Milde, Till, Jakobs, Martin, Fiesel, Petra, Fruehwald, Michael C., Driever, Pablo Hernaiz, Thomale, Ulrich W., Schuhmann, Martin U., Metzler, Markus, Bochennek, Konrad, Simon, Thorsten, Duerken, Matthias, Karremann, Michael ORCID: 0000-0002-9961-4752, Knirsch, Stephanie, Ebinger, Martin ORCID: 0000-0002-4229-8058, von Bueren, Andre O., Pietsch, Torsten, Herold-Mende, Christel, Reuss, David E., Kiening, Karl, Lichter, Peter, Eggert, Angelika, Kramm, Christof M., Pfister, Stefan M., Jones, David T. W., Baechli, Heidi and Witt, Olaf (2019). Brainstem biopsy in pediatric diffuse intrinsic pontine glioma in the era of precision medicine: the INFORM study experience. Eur. J. Cancer, 114. S. 27 - 36. OXFORD: ELSEVIER SCI LTD. ISSN 1879-0852

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Abstract

Purpose: Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive paediatric brain tumour with fatal outcome. The Individualised Therapy For Relapsed Malignancies In Childhood (INFORM) registry study offers comprehensive molecular profiling of high-risk tumours to identify target alterations for potential precision therapy. We analysed molecular characteristics and clinical data after brainstem biopsy of all enrolled newly diagnosed DIPGs. Patients and methods: From eFebruary 2015 to February 2018, 21 subsequent primary DIPG cases were enrolled in the nation-wide multicentre INFORM registry study after brainstem biopsy. Whole-genome, whole-exome sequencing and DNA methylation analysis were performed, and RNA-sequencing was added in case of sufficient material. Clinical data were obtained from standardised questionnaires and the INFORM clinical data bank. Results: Tumour material obtained from brainstem biopsy was sufficient for DNA analysis in all cases and RNA analysis in 16 of 21 cases. In 16 of 21 cases (76%), potential targetable alterations were identified including highly relevant MET and NTRK1 fusions as well as an EZH2 alteration not previously described in DIPG. In 5 of 21 cases, molecular information was used for initiation of targeted treatment. The majority of patients (19/21) presented with neurological deficits at diagnosis. Newly arising or worsening of neurological deficits postbiopsy occurred in nine patients. Symptoms were reversible or improved notably in eight cases. Conclusion: In this multicentre study setting, brainstem biopsy of DIPG was feasible and yielded sufficient material for comprehensive molecular profiling. Relevant molecular targets were identified impacting clinical management in a substantial subset. Death or severe bleeding occurred in none of the cases. One of 20 patients experienced unilateral paraesthesia possibly related to biopsy. (C) 2019 Elsevier Ltd. All rights reserved.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Pfaff, ElkeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
El Damaty, AhmedUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Balasubramanian, Gnana PrakashUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blattner-Johnson, MirjamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Worst, Barbara C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stark, SebastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Witt, HendrikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pajtler, Kristian W.UNSPECIFIEDorcid.org/0000-0002-3562-6121UNSPECIFIED
van Tilburg, Cornelis M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Witt, RuthUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Milde, TillUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jakobs, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fiesel, PetraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fruehwald, Michael C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Driever, Pablo HernaizUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thomale, Ulrich W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schuhmann, Martin U.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Metzler, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bochennek, KonradUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Simon, ThorstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Duerken, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Karremann, MichaelUNSPECIFIEDorcid.org/0000-0002-9961-4752UNSPECIFIED
Knirsch, StephanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ebinger, MartinUNSPECIFIEDorcid.org/0000-0002-4229-8058UNSPECIFIED
von Bueren, Andre O.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pietsch, TorstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Herold-Mende, ChristelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reuss, David E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kiening, KarlUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lichter, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eggert, AngelikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kramm, Christof M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pfister, Stefan M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jones, David T. W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baechli, HeidiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Witt, OlafUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-146941
DOI: 10.1016/j.ejca.2019.03.019
Journal or Publication Title: Eur. J. Cancer
Volume: 114
Page Range: S. 27 - 36
Date: 2019
Publisher: ELSEVIER SCI LTD
Place of Publication: OXFORD
ISSN: 1879-0852
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
HISTONE H3.3; MUTATIONS; CHILDREN; SUBGROUPS; CANCER; EZH2; METHYLATION; TUMORS; H3K27; TIMEMultiple languages
OncologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/14694

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