Integrated transcript and genome analyses reveal NKX2-1 and MEF2C as potential oncogenes in T-ALL

To identify novel 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.

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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