Integrated Transcript and Genome Analyses Reveal NKX2-1 and MEF2C as Potential Oncogenes in T Cell Acute Lymphoblastic Leukemia

被引：301

作者：

Homminga, Irene ^{[1
]}

Pieters, Rob ^{[1
]}

Langerak, Anton W. ^{[2
]}

de Rooi, Johan J. ^{[3
,4
]}

Stubbs, Andrew ^{[3
]}

Verstegen, Monique ^{[1
]}

Vuerhard, Maartje ^{[1
]}

Buijs-Gladdines, Jessica ^{[1
]}

Kooi, Clarissa ^{[1
]}

Klous, Petra ^{[5
,6
,7
]}

van Vlierberghe, Pieter ^{[8
]}

Ferrando, Adolfo A. ^{[9
]}

Cayuela, Jean Michel ^{[10
]}

Verhaaf, Brenda ^{[2
]}

Beverloo, H. Berna ^{[11
]}

Horstmann, Martin ^{[12
,13
,14
]}

de Haas, Valerie ^{[15
]}

Wiekmeijer, Anna-Sophia ^{[16
]}

Pike-Overzet, Karin ^{[16
]}

Staal, Frank J. T. ^{[16
]}

de Laat, Wouter ^{[5
,6
,7
]}

Soulier, Jean ^{[10
]}

Sigaux, Francois ^{[10
]}

Meijerink, Jules P. P. ^{[1
]}

机构：

[1] Erasmus MC Sophia Childrens Hosp, Dept Pediat Oncol Hematol, NL-3015 GJ Rotterdam, Netherlands

[2] Erasmus MC, Dept Immunol, NL-3015 GE Rotterdam, Netherlands

[3] Erasmus MC, Dept Bioinformat, NL-3015 GE Rotterdam, Netherlands

[4] Erasmus MC, Dept Biostat, NL-3015 GE Rotterdam, Netherlands

[5] Erasmus MC, Dept Cell Biol, NL-3015 GE Rotterdam, Netherlands

[6] Hubrecht Inst KNAW, NL-3584 CT Utrecht, Netherlands

[7] Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands

[8] Ghent Univ Hosp, Ctr Med Genet, B-9000 Ghent, Belgium

[9] Columbia Univ, Inst Canc Genet, New York, NY 10032 USA

[10] Univ Paris 07, Hop St Louis, Inst Univ Hematol, INSERM,U944, F-75010 Paris, France

[11] Erasmus MC, Dept Clin Genet, NL-3015 GE Rotterdam, Netherlands

[12] Res Inst Childrens Canc Ctr, D-20251 Hamburg, Germany

[13] Univ Med Ctr Hamburg Eppendorf, Clin Pediat Hematol & Oncol, D-20246 Hamburg, Germany

[14] Cooperat Study Grp Childhood Acute Lymphoblast Le, D-20246 Hamburg, Germany

[15] Dutch Childhood Oncol Grp DCOG, NL-2545 CJ The Hague, Netherlands

[16] Leiden Univ, Med Ctr, Dept Immunohematol & Blood Transfus, NL-2333 ZA Leiden, Netherlands

来源：

CANCER CELL | 2011年 / 19卷 / 04期

关键词：

GENE-EXPRESSION; ACTIVATION MECHANISM; TARGET GENE; C-MYC; FUSION; NOTCH1; IDENTIFICATION; TRANSFORMATION; PROLIFERATION; TRANSLOCATION;

D O I：

10.1016/j.ccr.2011.02.008

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

To identify oncogenic pathways in T cell acute lymphoblastic leukemia (T-ALL), we combined expression profiling of 117 pediatric patient samples and detailed molecular-cytogenetic analyses including the Chromosome Conformation Capture on Chip (4C) method. Two T-ALL subtypes were identified that lacked rearrangements of known oncogenes. One subtype associated with cortical arrest, expression of cell cycle genes, and ectopic NKX2-1 or NKX2-2 expression for which rearrangements were identified. The second subtype associated with immature T cell development and high expression of the MEF2C transcription factor as consequence of rearrangements of MEF2C, transcription factors that target MEF2C, or MEF2C-associated cofactors. We propose NKX2-1, NKX2-2, and MEF2C as T-ALL oncogenes that are activated by various rearrangements.

引用

页码：484 / 497

页数：14

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