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.
authors.affiliation: Department of Pediatric Oncology/Hematology, Erasmus MC/Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Irene
authors.initials: I
authors.lastname: Homminga
authors.forename: Rob
authors.initials: R
authors.lastname: Pieters
authors.forename: Anton W
authors.initials: AW
authors.lastname: Langerak
authors.forename: Johan J
authors.initials: JJ
authors.lastname: de Rooi
authors.forename: Andrew
authors.initials: A
authors.lastname: Stubbs
authors.forename: Monique
authors.initials: M
authors.lastname: Verstegen
authors.forename: Maartje
authors.initials: M
authors.lastname: Vuerhard
authors.forename: Jessica
authors.initials: J
authors.lastname: Buijs-Gladdines
authors.forename: Clarissa
authors.initials: C
authors.lastname: Kooi
authors.forename: Petra
authors.initials: P
authors.lastname: Klous
authors.forename: Pieter
authors.initials: P
authors.lastname: van Vlierberghe
authors.forename: Adolfo A
authors.initials: AA
authors.lastname: Ferrando
authors.forename: Jean Michel
authors.initials: JM
authors.lastname: Cayuela
authors.forename: Brenda
authors.initials: B
authors.lastname: Verhaaf
authors.forename: H Berna
authors.initials: HB
authors.lastname: Beverloo
authors.forename: Martin
authors.initials: M
authors.lastname: Horstmann
authors.forename: Valerie
authors.initials: V
authors.lastname: de Haas
authors.forename: Anna-Sophia
authors.initials: AS
authors.lastname: Wiekmeijer
authors.forename: Karin
authors.initials: K
authors.lastname: Pike-Overzet
authors.forename: Frank J T
authors.initials: FJ
authors.lastname: Staal
authors.forename: Wouter
authors.initials: W
authors.lastname: de Laat
authors.forename: Jean
authors.initials: J
authors.lastname: Soulier
authors.forename: Francois
authors.initials: F
authors.lastname: Sigaux
authors.forename: Jules P P
authors.initials: JP
authors.lastname: Meijerink
mesh_terms: D000293:Adolescent; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D015321:Gene Rearrangement; D015894:Genome, Human; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007223:Infant; D026161:MADS Domain Proteins / Q000235:genetics* / Q000502:physiology; D064326:MEF2 Transcription Factors; D008297:Male; D018006:Myogenic Regulatory Factors / Q000235:genetics* / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics* / Q000502:physiology; D009857:Oncogenes; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology; D014158:Transcription, Genetic; D029961:Zebrafish Proteins
chemical_list: D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; C578040:MEF2C protein, human; D018006:Myogenic Regulatory Factors; C000715631:NKX2-2 protein, human; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D029961:Zebrafish Proteins; C000715630:nkx2.2b protein, zebrafish