title: Molecular genetics of ependymomas and pediatric diffuse gliomas: a short review.
abstract: Here, we review the recent literature on molecular discoveries in ependymomas and pediatric diffuse gliomas. Ependymomas can now be categorized into three location-related subgroups according to their biological profile: posterior fossa ependymomas, group A (PFA) and B (PFB), and supratentorial ependymomas. Although no recurrently mutated genes were found throughout these groups of ependymomas, PFA exhibited a CpG island methylator phenotype, PFB was associated with extensive chromosomal aberrations, and the C11orf95-RELA fusion gene was frequently observed in supratentorial ependymomas. Meanwhile, it has now become apparent that pediatric diffuse gliomas have a distinct genetic status from their adult counterparts, even though they share an indistinguishable histology. In pediatric low-grade diffuse gliomas, an intragenic duplication of the portion of FGFR1 encoding the tyrosine kinase domain (TKD) and rearrangements of MYB/MYBL1 were found recurrently and mutually exclusively. As for non-brainstem high-grade tumors, in addition to H3F3A, TP53, and ATRX mutations, which were frequently observed in older children, recurrent fusions involving NTRK1, NTRK2, and NTRK3 were reported in infants younger than 3 years of age. Moreover, in diffuse intrinsic pontine gliomas (DIPG), recurrent somatic mutations of ACVR1 were found in association with HIST1H3B mutations.
authors.affiliation: Department of Human Pathology, Gunma University Graduate School of Medicine, 3-39-22, Showa-machi, Maebashi, Gunma, 371-8511, Japan, nobusawa0319@gunma-u.ac.jp.
authors.forename: Sumihito
authors.initials: S
authors.lastname: Nobusawa
authors.forename: Junko
authors.initials: J
authors.lastname: Hirato
authors.forename: Hideaki
authors.initials: H
authors.lastname: Yokoo
mesh_terms: D000293:Adolescent; D000367:Age Factors; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D004265:DNA Helicases / Q000235:genetics; D015257:DNA-Cytosine Methylases / Q000235:genetics; D004806:Ependymoma / Q000235:genetics* / Q000473:pathology; D020440:Gene Duplication; D050939:Gene Fusion; D015321:Gene Rearrangement; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007223:Infant; D015192:Infratentorial Neoplasms / Q000235:genetics* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011506:Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics; D020813:Receptor, trkB; D020812:Receptor, trkC / Q000235:genetics; D015173:Supratentorial Neoplasms / Q000235:genetics* / Q000473:pathology; D015534:Trans-Activators / Q000235:genetics; D051996:Transcription Factor RelA / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D000075924:X-linked Nuclear Protein; D055815:Young Adult; D014157:Transcription Factors
chemical_list: D004265:DNA Helicases; D015257:DNA-Cytosine Methylases; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; D011505:Protein-Tyrosine Kinases; D011506:Proteins; D011518:Proto-Oncogene Proteins; D051496:Receptor, Fibroblast Growth Factor, Type 1; D020813:Receptor, trkB; D020812:Receptor, trkC; D015534:Trans-Activators; D051996:Transcription Factor RelA; D016159:Tumor Suppressor Protein p53; D000075924:X-linked Nuclear Protein; C585140:ZFTA protein, human; D014157:Transcription Factors; C088831:MYBL1 protein, human; C498143:RELA protein, human; C495901:TP53 protein, human; C081573:DNA modification methylase SssI; C000591259:tropomyosin-related kinase-B, human; C092332:ATRX protein, human