@article{df453725f453458694e9a6f68a88cafc,
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 (∼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.",
keywords = "CELLCYCLE",
author = "Meihua Li and Lee, {Kyle F.} and Yuntao Lu and Ian Clarke and David Shih and Charles Eberhart and Collins, {V. Peter} and {Van Meter}, Tim and Daniel Picard and Limei Zhou and Boutros, {Paul C.} and Piergiorgio Modena and Liang, {Muh Lii} and Scherer, {Steve W.} and Eric Bouffet and Rutka, {James T.} and Pomeroy, {Scott L.} and Lau, {Ching C.} and Taylor, {Michael D.} and Amar Gajjar and Dirks, {Peter B.} and Hawkins, {Cynthia E.} and Annie Huang",
note = "Funding Information: We thank P. Burger, J. Squire, and L. Penn for mentorship; M. Massimo, L. Lafay-Cousin, M. Zielenska, S. Chilton, P. Northcott, P. Kongkam, T. Paton, and G. Casallo for generous help; J. Dick, S. Egan, C.C. Hui, E. Lechman, R. Gilbertson, and W. Halliday for helpful discussions; and P. Hu for statistical analysis. Funding from CBTF, SickKids (Brainchild), JM Foundations, and CCSRI (grant no. 17473) to A.H.; AIRC to P.M.; and tissue contributions from CHTN, NINDs, and the London Regional Brain Tumor Bank are gratefully acknowledged. M.L. was an ABTA Fellow; K.F.L. and D.S. received SickKids foundation RESTRACOMP predoctoral awards. M.L., K.F.L., Y.L., and D.S. performed all experiments and analyses with support from D.P., L.Z., and P.B. NSC studies were performed by I.C; E.B., P.M., M.L., P.C., M.C., T.V., S.P., C.E., and C.L. provided tumor tissue and clinical data. A.H. supervised the project. A.H., M.D.T., S.S., J.T.R., C.E.H., and P.B.D. contributed to manuscript writing and review. ",
year = "2009",
month = dec,
day = "8",
doi = "10.1016/j.ccr.2009.10.025",
language = "English (US)",
volume = "16",
pages = "533--546",
journal = "Cancer cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "6",
}