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

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgaveArtikelWetenschappelijkpeer review

Samenvatting

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-2Engels
Pagina's (van-tot)484-497
TijdschriftCancer Cell
Volume19
Nummer van het tijdschrift4
DOI's
StatusGepubliceerd - 2011

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