title: Novel genomic amplification targeting the microRNA cluster at 19q13.42 in a pediatric embryonal tumor with abundant neuropil and true rosettes.
abstract: Embryonal tumors with abundant neuropil and true rosettes (ETANTR) comprise a rare variant of embryonal brain tumors usually occurring in infants. Only 13 cases have been reported in the literature to date and little is known about the molecular pathogenesis of these tumors. Here, we describe a case of ETANTR in a 2-year-old girl presenting with a large tumor in the vermis of the cerebellum. Histological examination showed clusters of small-undifferentiated cells including ependymoblastic-like rosettes admixed with large fibrillar and paucicellular neuropil-like areas indicative for ETANTR. Genomic imbalances were detected by using array-based comparative genomic hybridization. In addition to trisomy of chromosome 2, which has been previously described in ETANTR, array-CGH revealed high-level genomic amplification of 0.89 Mb at chromosome band 19q13.42 covering a microRNA cluster and several protein-coding genes. This aberration has not been described in any other brain tumor to date, indicating a specific aberration in ETANTR. MicroRNAs contained in the microRNA cluster at 19q13.42 including oncomirs miRNA-372 and miRNA-373 were highly up-regulated in the tumor when compared to normal cerebellum or whole brain. In summary, this is the first report on a potentially specific genetic aberration in ETANTR, supporting the hypothesis of a distinct tumor entity.
authors.affiliation: Division Molecular Genetics, German Cancer Research Center, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. s.pfister@dkfz.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Pfister
authors.forename: Marc
authors.initials: M
authors.lastname: Remke
authors.forename: Mirco
authors.initials: M
authors.lastname: Castoldi
authors.forename: Alfa H C
authors.initials: AH
authors.lastname: Bai
authors.forename: Martina U
authors.initials: MU
authors.lastname: Muckenthaler
authors.forename: Andreas
authors.initials: A
authors.lastname: Kulozik
authors.forename: Andreas
authors.initials: A
authors.lastname: von Deimling
authors.forename: Armin
authors.initials: A
authors.lastname: Pscherer
authors.forename: Peter
authors.initials: P
authors.lastname: Lichter
authors.forename: Andrey
authors.initials: A
authors.lastname: Korshunov
mesh_terms: D002528:Cerebellar Neoplasms / Q000235:genetics* / Q000473:pathology; D002675:Child, Preschool; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D005260:Female; D005784:Gene Amplification; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D035683:MicroRNAs / Q000235:genetics*; D046228:Microarray Analysis; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger