Frequent amplification of a chr19q13.41 microRNA polycistron in aggressive primitive neuroectodermal brain tumors.
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.
Li
Meihua
M
Division of Hematology-Oncology, Hospital for Sick Children, Toronto, ON M5G 0A3, Canada.
Lee
Kyle F
KF
Lu
Yuntao
Y
Clarke
Ian
I
Shih
David
D
Eberhart
Charles
C
Collins
V Peter
VP
Van Meter
Tim
T
Picard
Daniel
D
Zhou
Limei
L
Boutros
Paul C
PC
Modena
Piergiorgio
P
Liang
Muh-Lii
ML
Scherer
Steve W
SW
Bouffet
Eric
E
Rutka
James T
JT
Pomeroy
Scott L
SL
Lau
Ching C
CC
Taylor
Michael D
MD
Gajjar
Amar
A
Dirks
Peter B
PB
Hawkins
Cynthia E
CE
Huang
Annie
A
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
D035683:MicroRNAs; D051153:Wnt Proteins