title: ETV6 mutations in early immature human T cell leukemias.
abstract: Early immature T cell acute lymphoblastic leukemias (T-ALLs) account for ~5-10% of pediatric T-ALLs and are associated with poor prognosis. However, the genetic defects that drive the biology of these tumors remain largely unknown. In this study, analysis of microarray gene expression signatures in adult T-ALL demonstrated a high prevalence of early immature leukemias and revealed a close relationship between these tumors and myeloid leukemias. Many adult immature T-ALLs harbored mutations in myeloid-specific oncogenes and tumor suppressors including IDH1, IDH2, DNMT3A, FLT3, and NRAS. Moreover, we identified ETV6 mutations as a novel genetic lesion uniquely present in immature adult T-ALL. Our results demonstrate that early immature adult T-ALL represents a heterogeneous category of leukemias characterized by the presence of overlapping myeloid and T-ALL characteristics, and highlight the potential role of ETV6 mutations in these tumors.
authors.affiliation: Institute for Cancer Genetics, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Pieter
authors.initials: P
authors.lastname: Van Vlierberghe
authors.forename: Alberto
authors.initials: A
authors.lastname: Ambesi-Impiombato
authors.forename: Arianne
authors.initials: A
authors.lastname: Perez-Garcia
authors.forename: J Erika
authors.initials: JE
authors.lastname: Haydu
authors.forename: Isaura
authors.initials: I
authors.lastname: Rigo
authors.forename: Michael
authors.initials: M
authors.lastname: Hadler
authors.forename: Valeria
authors.initials: V
authors.lastname: Tosello
authors.forename: Giusy
authors.initials: G
authors.lastname: Della Gatta
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Paietta
authors.forename: Janis
authors.initials: J
authors.lastname: Racevskis
authors.forename: Peter H
authors.initials: PH
authors.lastname: Wiernik
authors.forename: Selina M
authors.initials: SM
authors.lastname: Luger
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Rowe
authors.forename: Montserrat
authors.initials: M
authors.lastname: Rue
authors.forename: Adolfo A
authors.initials: AA
authors.lastname: Ferrando
mesh_terms: D000328:Adult; D045744:Cell Line, Tumor; D005260:Female; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic / Q000235:genetics; D016147:Genes, Tumor Suppressor; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics* / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism*; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D000097764:ETS Translocation Variant 6 Protein