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

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., Staal, F. J. T., de Laat, W., Soulier, J., Sigaux, F. & Meijerink, J. P. P., 12-Apr-2011, In : Cancer cell. 19, 4, p. 484-497 14 p.

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  • Integrated Transcript and Genome Analyses Reveal NKX2-1 and MEF2C

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DOI

  • 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

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 languageEnglish
Pages (from-to)484-497
Number of pages14
JournalCancer cell
Volume19
Issue number4
Publication statusPublished - 12-Apr-2011
Externally publishedYes

    Keywords

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

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