title: Focal genomic amplification at 19q13.42 comprises a powerful diagnostic marker for embryonal tumors with ependymoblastic rosettes.
abstract: Ependymoblastoma (EBL) and embryonal tumor with abundant neuropil and true rosettes (ETANTR) are very aggressive embryonal neoplasms characterized by the presence of ependymoblastic multilayered rosettes typically occurring in children below 6 years of age. It has not been established whether these two tumors really comprise distinct entities. Earlier, using array-CGH, we identified a unique focal amplification at 19q13.42 in a case of ETANTR. In the present study, we investigated this locus by fluorescence in situ hybridization in 41 tumors, which had morphologically been diagnosed as EBL or ETANTR. Strikingly, FISH analysis revealed 19q13.42 amplifications in 37/40 samples (93%). Among tumors harboring the amplification, 19 samples were identified as ETANTR and 18 as EBL. The three remaining tumors showed a polysomy of chromosome 19. Analysis of recurrent/metastatic tumors (n = 7) showed that the proportion of nuclei carrying the amplification was increased (up to 80-100% of nuclei) in comparison to the corresponding primary tumors. In conclusion, we have identified a hallmark cytogenetic aberration occurring in virtually all embryonal brain tumors with ependymoblastic rosettes suggesting that ETANTR and EBL comprise a single biological entity. FISH analysis of the 19q13.42 locus is a very promising diagnostic tool to identify a subset of primitive neuroectodermal tumors with distinct morphology, biology, and clinical behavior.
authors.affiliation: German Cancer Research Center, Heidelberg, Germany.
authors.forename: Andrey
authors.initials: A
authors.lastname: Korshunov
authors.forename: Marc
authors.initials: M
authors.lastname: Remke
authors.forename: Marco
authors.initials: M
authors.lastname: Gessi
authors.forename: Marina
authors.initials: M
authors.lastname: Ryzhova
authors.forename: Thomas
authors.initials: T
authors.lastname: Hielscher
authors.forename: Hendrik
authors.initials: H
authors.lastname: Witt
authors.forename: Vivienne
authors.initials: V
authors.lastname: Tobias
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Buccoliero
authors.forename: Iacopo
authors.initials: I
authors.lastname: Sardi
authors.forename: Marina Paola
authors.initials: MP
authors.lastname: Gardiman
authors.forename: Jose
authors.initials: J
authors.lastname: Bonnin
authors.forename: Bernd
authors.initials: B
authors.lastname: Scheithauer
authors.forename: Andreas E
authors.initials: AE
authors.lastname: Kulozik
authors.forename: Olaf
authors.initials: O
authors.lastname: Witt
authors.forename: Sverre
authors.initials: S
authors.lastname: Mork
authors.forename: Andreas
authors.initials: A
authors.lastname: von Deimling
authors.forename: Otmar D
authors.initials: OD
authors.lastname: Wiestler
authors.forename: Felice
authors.initials: F
authors.lastname: Giangaspero
authors.forename: Marc
authors.initials: M
authors.lastname: Rosenblum
authors.forename: Torsten
authors.initials: T
authors.lastname: Pietsch
authors.forename: Peter
authors.initials: P
authors.lastname: Lichter
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Pfister
mesh_terms: D002675:Child, Preschool; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007223:Infant; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D018242:Neuroectodermal Tumors, Primitive / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D016019:Survival Analysis