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.
N1 - Funding Information:
I.H. is financially supported by the Dutch Cancer Society (KWF-EMCR 2006-3500). C.K. and M.Ve. are financially supported by the Children Cancer Free Foundation (Stichting Kinderen Kankervrij, KiKa; Grant No. KiKa 2008-029). We also would like to thank the German Jose Carreras Leukemia Foundation (Grant No. SP 04/03), Children's Cancer Center Support Community Hamburg, and the French program Carte d'Identité des Tumeurs (CIT) from the Ligue Contre le Cancer for financial support.
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.
UR - http://www.scopus.com/inward/record.url?scp=79953735093&partnerID=8YFLogxK
U2 - 10.1016/j.ccr.2011.02.008
DO - 10.1016/j.ccr.2011.02.008
M3 - Article
C2 - 21481790
AN - SCOPUS:79953735093
SN - 1535-6108
VL - 19
SP - 484
EP - 497
JO - Cancer Cell
JF - Cancer Cell
IS - 4
ER -