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Frequent Amplification of a chr19q13.41 MicroRNA Polycistron in Aggressive Primitive Neuroectodermal Brain Tumors

2009; Cell Press; Volume: 16; Issue: 6 Linguagem: Inglês

10.1016/j.ccr.2009.10.025

1878-3686

Meihua Li, Kyle F. Lee, Yuntao Lu, Ian D. Clarke, David Shih, Charles G. Eberhart, V. Peter Collins, Timothy Van Meter, Daniel Picard, Limei Zhou, Paul C. Boutros, Piergiorgio Modena, Muh‐Lii Liang, Stephen W. Scherer, Éric Bouffet, James T. Rutka, Scott L. Pomeroy, Ching C. Lau, Michael D. Taylor, Amar Gajjar, Peter B. Dirks, Cynthia Hawkins, Annie Huang,

RNA Research and Splicing

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.