Rosette-forming glioneuronal tumors share a distinct DNA methylation profile and mutations in FGFR1, with recurrent co-mutation of PIK3CA and NF1

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Details zur Publikation

Autorinnen und Autoren: Sievers P, Appay R, Schrimpf D, Stichel D, Reuss DE, Wefers AK, Reinhardt A, Coras R, Ruf VC, Schmid S, de Stricker K, Boldt HB, Kristensen BW, Petersen JK, Ulhøi BP, Gardberg M, Aronica E, Hasselblatt M, Brück W, Bielle F, Mokhtari K, Lhermitte B, Wick W, Herold-Mende C, Hänggi D, Brandner S, Giangaspero F, Capper D, Rushing E, Wesseling P, Pfister SM, Figarella-Branger D, von Deimling A, Sahm F, Jones DT
Zeitschrift: Acta Neuropathologica
Jahr der Veröffentlichung: 2019
ISSN: 0001-6322
eISSN: 1432-0533


Abstract

Rosette-forming glioneuronal tumor (RGNT) is a rare brain neoplasm that primarily affects young adults. Although alterations affecting the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) signaling pathway have been associated with this low-grade entity, comprehensive molecular investigations of RGNT in larger series have not been performed to date, and an integrated view of their genetic and epigenetic profiles is still lacking. Here we describe a genome-wide DNA methylation and targeted sequencing-based characterization of a molecularly distinct class of tumors (n = 30), initially identified through genome-wide DNA methylation screening among a cohort of > 30,000 tumors, of which most were diagnosed histologically as RGNT. FGFR1 hotspot mutations were observed in all tumors analyzed, with co-occurrence of PIK3CA mutations in about two-thirds of the cases (63%). Additional loss-of-function mutations in the tumor suppressor gene NF1 were detected in a subset of cases (33%). Notably, in contrast to most other low-grade gliomas, these tumors often displayed co-occurrence of two or even all three of these mutations. Our data highlight that molecularly defined RGNTs are characterized by highly recurrent combined genetic alterations affecting both MAPK and PI3K signaling pathways. Thus, these two pathways appear to synergistically interact in the formation of RGNT, and offer potential therapeutic targets for this disease.


Einrichtungen weiterer Autorinnen und Autoren

Aarhus University Hospital / Aarhus Universitetshospital
Amsterdam UMC
Charité - Universitätsmedizin Berlin
Deutsches Krebsforschungszentrum (DKFZ)
Hôpital de Hautepierre
Hôpital de la Timone
Hopp-Kindertumorzentrum Heidelberg - KiTZ
Ludwig-Maximilians-Universität (LMU)
National Institute for Health and Medical Research / Institut national de la santé et de la recherche médicale (INSERM)
Odense Universitetshospital (OUH)
Rigshospitalet
Turku University Hospital / Turun yliopistollinen keskussairaala (TYKS)
Università degli studi "La Sapienza"
Universitätsklinikum Göttingen
Universitätsklinikum Heidelberg
Universitätsklinikum Mannheim
Universitätsklinikum Münster
Universitätsspital Zürich (USZ)
University College London (UCL)
University of Amsterdam


Zitierweisen

APA:
Sievers, P., Appay, R., Schrimpf, D., Stichel, D., Reuss, D.E., Wefers, A.K.,... Jones, D.T. (2019). Rosette-forming glioneuronal tumors share a distinct DNA methylation profile and mutations in FGFR1, with recurrent co-mutation of PIK3CA and NF1. Acta Neuropathologica. https://dx.doi.org/10.1007/s00401-019-02038-4

MLA:
Sievers, Philipp, et al. "Rosette-forming glioneuronal tumors share a distinct DNA methylation profile and mutations in FGFR1, with recurrent co-mutation of PIK3CA and NF1." Acta Neuropathologica (2019).

BibTeX: 

Zuletzt aktualisiert 2019-11-07 um 08:38