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

被引：195

作者：

Li, Meihua ^{[1
]}

Lee, Kyle F. ^{[1
]}

Lu, Yuntao ^{[1
,11
]}

Clarke, Ian ^{[2
]}

Shih, David ^{[1
]}

Eberhart, Charles ^{[6
]}

Collins, V. Peter ^{[7
]}

Van Meter, Tim ^{[8
]}

Picard, Daniel ^{[1
]}

Zhou, Limei ^{[1
]}

Boutros, Paul C. ^{[5
,8
]}

Modena, Piergiorgio ^{[9
]}

Liang, Muh-Lii ^{[10
]}

Scherer, Steve W. ^{[4
]}

Bouffet, Eric ^{[1
]}

Rutka, James T. ^{[2
]}

Pomeroy, Scott L. ^{[12
]}

Lau, Ching C. ^{[13
]}

Taylor, Michael D. ^{[2
]}

Gajjar, Amar ^{[14
]}

Dirks, Peter B. ^{[2
]}

Hawkins, Cynthia E. ^{[3
]}

Huang, Annie ^{[1
]}

机构：

[1] Hosp Sick Children, Div Hematol Oncol, Toronto, ON M5G 0A3, Canada

[2] Hosp Sick Children, Div Neurosurg, Toronto, ON M5G 0A3, Canada

[3] Hosp Sick Children, Dept Pathol, Toronto, ON M5G 0A3, Canada

[4] Hosp Sick Children, Ctr Appl Genom, Toronto, ON M5G 0A3, Canada

[5] Ontario Inst Canc Res, Toronto, ON M5G 1X8, Canada

[6] Johns Hopkins Univ, Sch Med, Div Pathol, Baltimore, MD 21205 USA

[7] Univ Cambridge, Div Pathol, Cambridge CB2 1TN, England

[8] Virginia Commonwealth Univ, Dept Neurosurg, Richmond, VA 23298 USA

[9] Ist Nazl Studio & Cura Tumori, I-210133 Milan, Italy

[10] Taiwan Vet Gen Hosp, Dept Neurosurg, Taipei 11217, Taiwan

[11] Nanfang Hosp, Dept Neurosurg, Guangzhou 510515, Guangdong, Peoples R China

[12] Childrens Hosp, Dept Neurol, Boston, MA 02115 USA

[13] Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA

[14] St Jude Childrens Res Hosp, Neurooncol Div, Memphis, TN 38105 USA

来源：

CANCER CELL | 2009年 / 16卷 / 06期

关键词：

NERVOUS-SYSTEM; STEM-CELLS; YOUNG-CHILDREN; SUPRATENTORIAL; EXPRESSION; SURVIVAL; CANCER; GENE; MEDULLOBLASTOMAS; DIFFERENTIATION;

D O I：

10.1016/j.ccr.2009.10.025

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

We discovered a high-level amplicon involving the chr19q13.41 microRNA (miRNA) cluster (C19MC) in 11/45 (similar to 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.

引用

页码：533 / 546

页数：14

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