title: Frequent amplification of a chr19q13.41 microRNA polycistron in aggressive primitive neuroectodermal brain tumors.
abstract: We discovered a high-level amplicon involving the chr19q13.41 microRNA (miRNA) cluster (C19MC) in 11/45 ( approximately 25%) primary CNS-PNET, which results in striking overexpression of miR-517c and 520g. Constitutive expression of miR-517c or 520g promotes in vitro and in vivo oncogenicity, modulates cell survival, and robustly enhances growth of untransformed human neural stem cells (hNSCs) in part by upregulating WNT pathway signaling and restricting differentiation of hNSCs. Remarkably, the C19MC amplicon, which is very rare in other brain tumors (1/263), identifies an aggressive subgroup of CNS-PNET with distinct gene-expression profiles, characteristic histology, and dismal survival. Our data implicate miR-517c and 520g as oncogenes and promising biological markers for CNS-PNET and provide important insights into oncogenic properties of the C19MC locus.
authors: Division of Hematology-Oncology, Hospital for Sick Children, Toronto, ON M5G 0A3, Canada.
authors: Meihua
authors: M
authors: Li
authors: Kyle F
authors: KF
authors: Lee
authors: Yuntao
authors: Y
authors: Lu
authors: Ian
authors: I
authors: Clarke
authors: David
authors: D
authors: Shih
authors: Charles
authors: C
authors: Eberhart
authors: V Peter
authors: VP
authors: Collins
authors: Tim
authors: T
authors: Van Meter
authors: Daniel
authors: D
authors: Picard
authors: Limei
authors: L
authors: Zhou
authors: Paul C
authors: PC
authors: Boutros
authors: Piergiorgio
authors: P
authors: Modena
authors: Muh-Lii
authors: ML
authors: Liang
authors: Steve W
authors: SW
authors: Scherer
authors: Eric
authors: E
authors: Bouffet
authors: James T
authors: JT
authors: Rutka
authors: Scott L
authors: SL
authors: Pomeroy
authors: Ching C
authors: CC
authors: Lau
authors: Michael D
authors: MD
authors: Taylor
authors: Amar
authors: A
authors: Gajjar
authors: Peter B
authors: PB
authors: Dirks
authors: Cynthia E
authors: CE
authors: Hawkins
authors: Annie
authors: A
authors: Huang
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002454:Cell Differentiation; D002888:Chromosomes, Human, Pair 19; D005784:Gene Amplification; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D018242:Neuroectodermal Tumors, Primitive / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction; D013234:Stem Cells; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D051153:Wnt Proteins