Identification of OTX2 as a medulloblastoma oncogene whose product can be targeted by all-trans retinoic acid

Chunhui Di; Shaoxi Liao; David C. Adamson; Timothy J. Parrett; Daniel K. Broderick; Qun Shi; Christoph Lengauer; Jordan M. Cummins; Victor E. Velculescu; Daniel W. Fults; Roger E. McLendon; Darell D. Bigner; Hai Yan

Identification of OTX2 as a medulloblastoma oncogene whose product can be targeted by all-trans retinoic acid

Chunhui Di, Shaoxi Liao, David C. Adamson, Timothy J. Parrett, Daniel K. Broderick, Qun Shi, Christoph Lengauer, Jordan M. Cummins, Victor E. Velculescu, Daniel W. Fults, Roger E. McLendon, Darell D. Bigner, Hai Yan

School of Medicine

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

123 Scopus citations

Abstract

Through digital karyotyping of permanent medulloblastoma cell lines, we found that the homeobox gene OTX2 was amplified more than 10-fold in three cell lines. Gene expression analyses showed that OTX2 transcripts were present at high levels in 14 of 15 (93%) medulloblastomas with anaplastic histopathologic features. Knockdown of OTX2 expression by siRNAs inhibited medulloblastoma cell growth in vitro, whereas pharmacologic doses of all-trans retinoic acid repressed OTX2 expression and induced apoptosis only in medulloblastoma cell lines that expressed OTX2. These observations suggest that OTX2 is essential for the pathogenesis of anaplastic medulloblastomas and that these tumors may be amenable to therapy with all-trans-retinoic acid.

Original language	English (US)
Pages (from-to)	919-924
Number of pages	6
Journal	Cancer Research
Volume	65
Issue number	3
State	Published - Feb 1 2005

ASJC Scopus subject areas

Oncology
Cancer Research

Cite this

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title = "Identification of OTX2 as a medulloblastoma oncogene whose product can be targeted by all-trans retinoic acid",

abstract = "Through digital karyotyping of permanent medulloblastoma cell lines, we found that the homeobox gene OTX2 was amplified more than 10-fold in three cell lines. Gene expression analyses showed that OTX2 transcripts were present at high levels in 14 of 15 (93%) medulloblastomas with anaplastic histopathologic features. Knockdown of OTX2 expression by siRNAs inhibited medulloblastoma cell growth in vitro, whereas pharmacologic doses of all-trans retinoic acid repressed OTX2 expression and induced apoptosis only in medulloblastoma cell lines that expressed OTX2. These observations suggest that OTX2 is essential for the pathogenesis of anaplastic medulloblastomas and that these tumors may be amenable to therapy with all-trans-retinoic acid.",

author = "Chunhui Di and Shaoxi Liao and Adamson, {David C.} and Parrett, {Timothy J.} and Broderick, {Daniel K.} and Qun Shi and Christoph Lengauer and Cummins, {Jordan M.} and Velculescu, {Victor E.} and Fults, {Daniel W.} and McLendon, {Roger E.} and Bigner, {Darell D.} and Hai Yan",

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journal = "Cancer Research",

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TY - JOUR

T1 - Identification of OTX2 as a medulloblastoma oncogene whose product can be targeted by all-trans retinoic acid

AU - Di, Chunhui

AU - Liao, Shaoxi

AU - Adamson, David C.

AU - Parrett, Timothy J.

AU - Broderick, Daniel K.

AU - Shi, Qun

AU - Lengauer, Christoph

AU - Cummins, Jordan M.

AU - Velculescu, Victor E.

AU - Fults, Daniel W.

AU - McLendon, Roger E.

AU - Bigner, Darell D.

AU - Yan, Hai

PY - 2005/2/1

Y1 - 2005/2/1

N2 - Through digital karyotyping of permanent medulloblastoma cell lines, we found that the homeobox gene OTX2 was amplified more than 10-fold in three cell lines. Gene expression analyses showed that OTX2 transcripts were present at high levels in 14 of 15 (93%) medulloblastomas with anaplastic histopathologic features. Knockdown of OTX2 expression by siRNAs inhibited medulloblastoma cell growth in vitro, whereas pharmacologic doses of all-trans retinoic acid repressed OTX2 expression and induced apoptosis only in medulloblastoma cell lines that expressed OTX2. These observations suggest that OTX2 is essential for the pathogenesis of anaplastic medulloblastomas and that these tumors may be amenable to therapy with all-trans-retinoic acid.

AB - Through digital karyotyping of permanent medulloblastoma cell lines, we found that the homeobox gene OTX2 was amplified more than 10-fold in three cell lines. Gene expression analyses showed that OTX2 transcripts were present at high levels in 14 of 15 (93%) medulloblastomas with anaplastic histopathologic features. Knockdown of OTX2 expression by siRNAs inhibited medulloblastoma cell growth in vitro, whereas pharmacologic doses of all-trans retinoic acid repressed OTX2 expression and induced apoptosis only in medulloblastoma cell lines that expressed OTX2. These observations suggest that OTX2 is essential for the pathogenesis of anaplastic medulloblastomas and that these tumors may be amenable to therapy with all-trans-retinoic acid.

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Identification of OTX2 as a medulloblastoma oncogene whose product can be targeted by all-trans retinoic acid

Abstract

ASJC Scopus subject areas

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