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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)533-546
Number of pages14
JournalCancer cell
Volume16
Issue number6
DOIs
StatePublished - Dec 8 2009

Keywords

  • CELLCYCLE

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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