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 Gajjar; Peter B. Dirks; Cynthia E. Hawkins; Annie Huang

doi:10.1016/j.ccr.2009.10.025

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

173 Scopus citations

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 language	English (US)
Pages (from-to)	533-546
Number of pages	14
Journal	Cancer cell
Volume	16
Issue number	6
DOIs	https://doi.org/10.1016/j.ccr.2009.10.025
State	Published - Dec 8 2009

Keywords

CELLCYCLE

ASJC Scopus subject areas

Oncology
Cell Biology
Cancer Research

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10.1016/j.ccr.2009.10.025

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Li, M., Lee, K. F., Lu, Y., Clarke, I., Shih, D., Eberhart, C., Collins, V. P., Van Meter, T., Picard, D., Zhou, L., Boutros, P. C., Modena, P., Liang, M. L., Scherer, S. W., Bouffet, E., Rutka, J. T., Pomeroy, S. L., Lau, C. C., Taylor, M. D., ... Huang, A. (2009). Frequent Amplification of a chr19q13.41 MicroRNA Polycistron in Aggressive Primitive Neuroectodermal Brain Tumors. Cancer cell, 16(6), 533-546. https://doi.org/10.1016/j.ccr.2009.10.025

Li, M, Lee, KF, Lu, Y, Clarke, I, Shih, D, Eberhart, C, Collins, VP, Van Meter, T, Picard, D, Zhou, L, Boutros, PC, Modena, P, Liang, ML, Scherer, SW, Bouffet, E, Rutka, JT, Pomeroy, SL, Lau, CC, Taylor, MD, Gajjar, A, Dirks, PB, Hawkins, CE & Huang, A 2009, 'Frequent Amplification of a chr19q13.41 MicroRNA Polycistron in Aggressive Primitive Neuroectodermal Brain Tumors', Cancer cell, vol. 16, no. 6, pp. 533-546. https://doi.org/10.1016/j.ccr.2009.10.025

@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",

}

TY - JOUR

T1 - Frequent Amplification of a chr19q13.41 MicroRNA Polycistron in Aggressive Primitive Neuroectodermal Brain Tumors

AU - Li, Meihua

AU - Lee, Kyle F.

AU - Lu, Yuntao

AU - Clarke, Ian

AU - Shih, David

AU - Eberhart, Charles

AU - Collins, V. Peter

AU - Van Meter, Tim

AU - Picard, Daniel

AU - Zhou, Limei

AU - Boutros, Paul C.

AU - Modena, Piergiorgio

AU - Liang, Muh Lii

AU - Scherer, Steve W.

AU - Bouffet, Eric

AU - Rutka, James T.

AU - Pomeroy, Scott L.

AU - Lau, Ching C.

AU - Taylor, Michael D.

AU - Gajjar, Amar

AU - Dirks, Peter B.

AU - Hawkins, Cynthia E.

AU - Huang, Annie

N1 - 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.

PY - 2009/12/8

Y1 - 2009/12/8

N2 - 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.

AB - 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.

KW - CELLCYCLE

UR - http://www.scopus.com/inward/record.url?scp=70749095079&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70749095079&partnerID=8YFLogxK

U2 - 10.1016/j.ccr.2009.10.025

DO - 10.1016/j.ccr.2009.10.025

M3 - Article

C2 - 19962671

AN - SCOPUS:70749095079

SN - 1535-6108

VL - 16

SP - 533

EP - 546

JO - Cancer cell

JF - Cancer cell

IS - 6

ER -

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

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