A comprehensive analysis of infantile central nervous system tumors to improve distinctive criteria for infant-type hemispheric glioma versus desmoplastic infantile ganglioglioma/astrocytoma

被引：9

作者：

Tauziede-Espariat, Arnault ^{[1
,2
,18
]}

Beccaria, Kevin ^{[3
]}

Dangouloff-Ros, Volodia ^{[4
,5
,6
]}

Sievers, Philipp ^{[7
,8
]}

Meurgey, Alexandra ^{[9
,10
]}

Pissaloux, Daniel ^{[9
,10
]}

Appay, Romain ^{[11
,12
]}

Saffroy, Raphael ^{[13
]}

Grill, Jacques ^{[14
,15
]}

Mariet, Cassandra ^{[15
]}

Bourdeaut, Franck ^{[16
,17
]}

Hasty, Lauren ^{[1
]}

Metais, Alice ^{[1
,2
]}

Chretien, Fabrice ^{[1
]}

Blauwblomme, Thomas

Puget, Stephanie ^{[4
]}

Boddaert, Nathalie ^{[4
,5
,6
]}

Varlet, Pascale ^{[1
,2
]}

机构：

[1] St Anne Hosp, Dept Neuropathol, GHU Paris Psychiat & Neurosci, Paris, France

[2] Inst Psychiat & Neurosci Paris, Inserm, UMR 1266, IMA Brain, Paris, France

[3] Univ Paris 05, Necker Hosp, APHP, Dept Pediat Neurosurg,Sorbonne Paris Cite, Paris, France

[4] Hop Necker Enfants Malad, AP HP, Pediat Radiol Dept, Paris, France

[5] Univ Paris Cite, Inst Imagine, UMR 1163, Paris, France

[6] INSERM U1299, Paris, France

[7] Univ Hosp Heidelberg, Inst Pathol, Dept Neuropathol, Heidelberg, Germany

[8] German Canc Res Ctr, Clin Cooperat Unit Neuropathol, German Consortium Translat Canc Res DKTK, Heidelberg, Germany

[9] Leon Berard Canc Ctr, Dept Biopathol, Lyon, France

[10] Canc Res Ctr Lyon CRCL, INSERM 1052, CNRS 5286, Lyon, France

[11] CHU Timone, APHM, Serv Anat Pathol & Neuropathol, Marseille, France

[12] Aix Marseille Univ, Inst Neurophysiopathol, CNRS, INP, Marseille, France

[13] Hop Paul Brousse, Dept Biochem & Oncogenet, Villejuif, France

[14] Univ Paris Saclay, U981, Mol Predictors & New Targets Oncol, INSERM,Gustave Roussy, Villejuif, France

[15] Univ Paris Saclay, Dept Pediat Oncol, Gustave Roussy, Villejuif, France

[16] Lab Translat Res Pediat Oncol, INSERMU830, Paris, France

[17] Paris Sci Lettres Res Univ, Inst Curie, SIREDO Ctr Care Innovat Res Pediat Adolescent & Yo, Paris, France

[18] St Anne Hosp, GHU Paris Psychiat & Neurosci, Dept Neuropathol, 1 Rue Cabanis, F-75014 Paris, France

来源：

BRAIN PATHOLOGY | 2023年 / 33卷 / 05期

关键词：

desmoplastic infantile ganglioglioma; astrocytoma; DNA-methylation; infantile; infant-type hemispheric glioma; EXPRESSION;

D O I：

10.1111/bpa.13182

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Recent epigenomic analyses have revealed the existence of a new DNA methylation class (MC) of infant-type hemispheric glioma (IHG). Like desmoplastic infantile ganglioglioma/astrocytoma (DIG/DIA), these tumors mainly affect infants and are supratentorial. While DIG/DIA is characterized by BRAF or RAF1 alterations, IHG has been shown to have receptor tyrosine kinase (RTK) gene fusions (ALK, ROS1, NTRK1/2/3, and MET). However, in this rapidly evolving field, a more comprehensive analysis of infantile glial/glioneuronal tumors including clinical, radiological, histopathological, and molecular data is needed. Here, we retrospectively investigated data from 30 infantile glial/glioneuronal tumors, consecutively compiled from our center. They were analyzed by two experienced pediatric neuroradiologists in consensus, without former knowledge of the molecular data. We also performed a comprehensive clinical, and histopathological examination (including molecular evaluation by next-generation sequencing, RNA sequencing, and fluorescence in situ hybridization [FISH] analyses), as well as DNA methylation profiling for the samples having sufficient material available. The integrative histopathological, genetic, and epigenetic analyses, including t-distributed stochastic neighbor embedding (t-SNE) analyses segregated tumors into 10 DIG/DIA (33.3%), six IHG (20.0%), three gangliogliomas (10.0%), two pleomorphic xanthoastrocytomas (6.7%), two pilocytic astrocytomas (6.7%), two supratentorial ependymomas, ZFTA fusion-positive (6.7%), two supratentorial ependymomas, YAP1 fusion-positive (6.7%), two embryonal tumors with PLAGL2-family amplification (6.7%), and one diffuse low-grade glioma, MAPK-pathway altered. This study highlights the significant differential features, in terms of histopathology (leptomeningeal infiltration, intense desmoplasia and ganglion cells in DIG/DIA and necrosis, microvascular proliferation, and siderophages in IHG), and radiology between DIG/DIA and IHG. Moreover, these results are consistent with the literature data concerning the molecular dichotomy (BRAF/RAF1 alterations vs. RTK genes' fusions) between DIG/DIA and IHG. This study characterized histopathologically and radiologically two additional cases of the novel embryonal tumor characterized by PLAGL2 gene amplification.

引用

页数：16