Integrated transcript and genome analyses reveal NKX2-1 and MEF2C as potential oncogenes in T cell acute lymphoblastic leukemia

I. Homminga; R. Pieters; A.W. Langerak; J.J. de Rooi; A. Stubbs; M. Verstegen; M. Vuerhard; J. Buijs-Gladdines; C. Kooi; P. Klous; P. van Vlierberghe; A.A. Ferrando; J.M. Cayuela; B. Verhaaf; H.B. Beverloo; M. Horstmann; V. de Haas; A.S. Wiekmeijer; K. Pike-Overzet; F.J. Staal; W. de Laat; J. Soulier; F. Sigaux; J.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

I. Homminga, R. Pieters, A.W. Langerak, J.J. de Rooi, A. Stubbs, M. Verstegen, M. Vuerhard, J. Buijs-Gladdines, C. Kooi, P. Klous, P. van Vlierberghe, A.A. Ferrando, J.M. Cayuela, B. Verhaaf, H.B. Beverloo, M. Horstmann, V. de Haas, A.S. Wiekmeijer, K. Pike-Overzet, F.J. StaalW. de Laat, J. Soulier, F. Sigaux, J.P. Meijerink

Hubrecht Institute

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Artikel › Wetenschappelijk › peer review

302 Citaten (Scopus)

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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: Adolescent, Cell Proliferation, Child, Child, Preschool, Cluster Analysis, Female, Gene Expression Regulation, Leukemic, Gene Rearrangement, Genome, Human, Homeodomain Proteins/ genetics/physiology, Humans, Infant, MADS Domain Proteins/ genetics/physiology, Male, Myogenic Regulatory Factors/ genetics/physiology, Nuclear Proteins/ genetics/physiology, Oncogenes, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/etiology/ genetics/pathology, Transcription Factors/ genetics/physiology, Tr

Originele taal-2	Engels
Pagina's (van-tot)	484-497
Tijdschrift	Cancer Cell
Volume	19
Nummer van het tijdschrift	4
DOI's	https://doi.org/10.1016/j.ccr.2011.02.008
Status	Gepubliceerd - 2011

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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. (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{e733ffbf6b7140e5b7996dd3c9fd1579,

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: Adolescent, Cell Proliferation, Child, Child, Preschool, Cluster Analysis, Female, Gene Expression Regulation, Leukemic, Gene Rearrangement, Genome, Human, Homeodomain Proteins/ genetics/physiology, Humans, Infant, MADS Domain Proteins/ genetics/physiology, Male, Myogenic Regulatory Factors/ genetics/physiology, Nuclear Proteins/ genetics/physiology, Oncogenes, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/etiology/ genetics/pathology, Transcription Factors/ genetics/physiology, Tr",

author = "I. Homminga and R. Pieters and A.W. Langerak and {de Rooi}, J.J. and A. Stubbs and M. Verstegen and M. Vuerhard and J. Buijs-Gladdines and C. Kooi and P. Klous and {van Vlierberghe}, P. and A.A. Ferrando and J.M. Cayuela and B. Verhaaf and H.B. Beverloo and M. Horstmann and {de Haas}, V. and A.S. Wiekmeijer and K. Pike-Overzet and F.J. Staal and {de Laat}, W. and J. Soulier and F. Sigaux and J.P. Meijerink",

note = "Reporting year: 2011",

year = "2011",

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, AS, Pike-Overzet, K, Staal, FJ, de Laat, W, Soulier, J, Sigaux, F & Meijerink, JP 2011, 'Integrated transcript and genome analyses reveal NKX2-1 and MEF2C as potential oncogenes in T cell acute lymphoblastic leukemia', Cancer Cell, vol. 19, nr. 4, blz. 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, I.

AU - Pieters, R.

AU - Langerak, A.W.

AU - de Rooi, J.J.

AU - Stubbs, A.

AU - Verstegen, M.

AU - Vuerhard, M.

AU - Buijs-Gladdines, J.

AU - Kooi, C.

AU - Klous, P.

AU - van Vlierberghe, P.

AU - Ferrando, A.A.

AU - Cayuela, J.M.

AU - Verhaaf, B.

AU - Beverloo, H.B.

AU - Horstmann, M.

AU - de Haas, V.

AU - Wiekmeijer, A.S.

AU - Pike-Overzet, K.

AU - Staal, F.J.

AU - de Laat, W.

AU - Soulier, J.

AU - Sigaux, F.

AU - Meijerink, J.P.

N1 - Reporting year: 2011

PY - 2011

Y1 - 2011

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. [KEYWORDS: Adolescent, Cell Proliferation, Child, Child, Preschool, Cluster Analysis, Female, Gene Expression Regulation, Leukemic, Gene Rearrangement, Genome, Human, Homeodomain Proteins/ genetics/physiology, Humans, Infant, MADS Domain Proteins/ genetics/physiology, Male, Myogenic Regulatory Factors/ genetics/physiology, Nuclear Proteins/ genetics/physiology, Oncogenes, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/etiology/ genetics/pathology, Transcription Factors/ genetics/physiology, Tr

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. [KEYWORDS: Adolescent, Cell Proliferation, Child, Child, Preschool, Cluster Analysis, Female, Gene Expression Regulation, Leukemic, Gene Rearrangement, Genome, Human, Homeodomain Proteins/ genetics/physiology, Humans, Infant, MADS Domain Proteins/ genetics/physiology, Male, Myogenic Regulatory Factors/ genetics/physiology, Nuclear Proteins/ genetics/physiology, Oncogenes, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/etiology/ genetics/pathology, Transcription Factors/ genetics/physiology, Tr

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

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