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

Irene Homminga; Rob Pieters; Anton W. Langerak; Johan J. de Rooi; Andrew Stubbs; Monique Verstegen; Maartje Vuerhard; Jessica Buijs-Gladdines; Clarissa Kooi; Petra Klous; Pieter van Vlierberghe; Adolfo A. Ferrando; Jean Michel Cayuela; Brenda Verhaaf; H. Berna Beverloo; Martin Horstmann; Valerie de Haas; Anna-Sophia Wiekmeijer; Karin Pike-Overzet; Frank J. T. Staal; Wouter de Laat; Jean Soulier; Francois Sigaux; Jules P. P. Meijerink

doi:10.1016/j.ccr.2011.02.008

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

Irene Homminga, Rob Pieters, Anton W. Langerak, Johan J. de Rooi, Andrew Stubbs, Monique Verstegen, Maartje Vuerhard, Jessica Buijs-Gladdines, Clarissa Kooi, Petra Klous, Pieter van Vlierberghe, Adolfo A. Ferrando, Jean Michel Cayuela, Brenda Verhaaf, H. Berna Beverloo, Martin Horstmann, Valerie de Haas, Anna-Sophia Wiekmeijer, Karin Pike-Overzet, Frank J. T. StaalWouter de Laat, Jean Soulier, Francois Sigaux, Jules P. P. Meijerink^*

^*Corresponding author for this work

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

318 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	484-497
Number of pages	14
Journal	Cancer cell
Volume	19
Issue number	4
DOIs	https://doi.org/10.1016/j.ccr.2011.02.008
Publication status	Published - 12-Apr-2011
Externally published	Yes

Keywords

GENE-EXPRESSION
ACTIVATION MECHANISM
HOMEOBOX GENE
TARGET GENE
C-MYC
FUSION
CANCER
NOTCH1
IDENTIFICATION
TRANSFORMATION

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Integrated Transcript and Genome Analyses Reveal NKX2-1 and MEF2C
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Homminga, I., Pieters, R., Langerak, A. W., de Rooi, J. J., Stubbs, A., Verstegen, M., Vuerhard, M., Buijs-Gladdines, J., Kooi, C., Klous, P., van Vlierberghe, P., Ferrando, A. A., Cayuela, J. M., Verhaaf, B., Beverloo, H. B., Horstmann, M., de Haas, V., Wiekmeijer, A.-S., Pike-Overzet, K., ... Meijerink, J. P. P. (2011). Integrated Transcript and Genome Analyses Reveal NKX2-1 and MEF2C as Potential Oncogenes in T Cell Acute Lymphoblastic Leukemia. Cancer cell, 19(4), 484-497. https://doi.org/10.1016/j.ccr.2011.02.008

@article{6c2671587bc04ccdabefa090f02490d1,

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

abstract = "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.",

keywords = "GENE-EXPRESSION, ACTIVATION MECHANISM, HOMEOBOX GENE, TARGET GENE, C-MYC, FUSION, CANCER, NOTCH1, IDENTIFICATION, TRANSFORMATION",

author = "Irene Homminga and Rob Pieters and Langerak, {Anton W.} and {de Rooi}, {Johan J.} and Andrew Stubbs and Monique Verstegen and Maartje Vuerhard and Jessica Buijs-Gladdines and Clarissa Kooi and Petra Klous and {van Vlierberghe}, Pieter and Ferrando, {Adolfo A.} and Cayuela, {Jean Michel} and Brenda Verhaaf and Beverloo, {H. Berna} and Martin Horstmann and {de Haas}, Valerie and Anna-Sophia Wiekmeijer and Karin Pike-Overzet and Staal, {Frank J. T.} and {de Laat}, Wouter and Jean Soulier and Francois Sigaux and Meijerink, {Jules P. P.}",

year = "2011",

month = apr,

day = "12",

doi = "10.1016/j.ccr.2011.02.008",

language = "English",

volume = "19",

pages = "484--497",

journal = "Cancer cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "4",

}

Homminga, I, Pieters, R, Langerak, AW, de Rooi, JJ, Stubbs, A, Verstegen, M, Vuerhard, M, Buijs-Gladdines, J, Kooi, C, Klous, P, van Vlierberghe, P, Ferrando, AA, Cayuela, JM, Verhaaf, B, Beverloo, HB, Horstmann, M, de Haas, V, Wiekmeijer, A-S, Pike-Overzet, K, Staal, FJT, de Laat, W, Soulier, J, Sigaux, F & Meijerink, JPP 2011, 'Integrated Transcript and Genome Analyses Reveal NKX2-1 and MEF2C as Potential Oncogenes in T Cell Acute Lymphoblastic Leukemia', Cancer cell, vol. 19, no. 4, pp. 484-497. https://doi.org/10.1016/j.ccr.2011.02.008

TY - JOUR

T1 - Integrated Transcript and Genome Analyses Reveal NKX2-1 and MEF2C as Potential Oncogenes in T Cell Acute Lymphoblastic Leukemia

AU - Homminga, Irene

AU - Pieters, Rob

AU - Langerak, Anton W.

AU - de Rooi, Johan J.

AU - Stubbs, Andrew

AU - Verstegen, Monique

AU - Vuerhard, Maartje

AU - Buijs-Gladdines, Jessica

AU - Kooi, Clarissa

AU - Klous, Petra

AU - van Vlierberghe, Pieter

AU - Ferrando, Adolfo A.

AU - Cayuela, Jean Michel

AU - Verhaaf, Brenda

AU - Beverloo, H. Berna

AU - Horstmann, Martin

AU - de Haas, Valerie

AU - Wiekmeijer, Anna-Sophia

AU - Pike-Overzet, Karin

AU - Staal, Frank J. T.

AU - de Laat, Wouter

AU - Soulier, Jean

AU - Sigaux, Francois

AU - Meijerink, Jules P. P.

PY - 2011/4/12

Y1 - 2011/4/12

N2 - 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.

AB - 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.

KW - GENE-EXPRESSION

KW - ACTIVATION MECHANISM

KW - HOMEOBOX GENE

KW - TARGET GENE

KW - C-MYC

KW - FUSION

KW - CANCER

KW - NOTCH1

KW - IDENTIFICATION

KW - TRANSFORMATION

U2 - 10.1016/j.ccr.2011.02.008

DO - 10.1016/j.ccr.2011.02.008

M3 - Article

SN - 1535-6108

VL - 19

SP - 484

EP - 497

JO - Cancer cell

JF - Cancer cell

IS - 4

ER -

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

Abstract

Keywords

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