title: Biallelic alterations of both ETV6 and CDKN1B genes in a t(12;21) childhood acute lymphoblastic leukemia case.
abstract: Recently, a new recurrent t(12;21)(pl3;q22) has been identified in a B-cell lineage childhood acute lymphoblastic leukemia (ALL). The translocation results in a fusion of two known genes, ETV6/TEL (12p13) and AML1 (21q22), previously shown to be involved in the pathogenesis of myeloid disorders. We report results of cytogenetic fluorescence in situ hybridization and molecular studies of a B-cell childhood common ALL with a cryptic 12;21 translocation. Aberrations identified in this case involve both chromosomes 12 and include not only the ETV6-AML1 gene fusion and two different microdeletions of ETV6 but also the hemizygous loss of CDKN1B, D12S119, and KRAS2 loci and a putative rearrangement of the second CDKN1B allele as a result of an inv(12)(p13q24). Moreover, it was shown that the AML1-ETV6 reciprocal chimeric transcript was not present in the malignant cells, and hence may not play a major role in leukemogenesis. In addition, the putative loss of wild-type function of CDKN1B and ETV6 could indicate a synergistic effect of both genes in the pathogenesis of this leukemia case.
authors.affiliation: Center for Human Genetics, Flanders Interuniversity Institute for Biotechnology, Leuven, Belgium.
authors.forename: I
authors.initials: I
authors.lastname: Wlodarska
authors.forename: M
authors.initials: M
authors.lastname: Baens
authors.forename: P
authors.initials: P
authors.lastname: Peeters
authors.forename: J
authors.initials: J
authors.lastname: Aerssens
authors.forename: C
authors.initials: C
authors.lastname: Mecucci
authors.forename: P
authors.initials: P
authors.lastname: Brock
authors.forename: P
authors.initials: P
authors.lastname: Marynen
authors.forename: H
authors.initials: H
authors.lastname: Van den Berghe
mesh_terms: D000293:Adolescent; D000483:Alleles; D001483:Base Sequence; D002869:Chromosome Aberrations / Q000235:genetics*; D002871:Chromosome Banding; D002872:Chromosome Deletion; D025063:Chromosome Disorders; D002881:Chromosomes, Human, Pair 12; D002891:Chromosomes, Human, Pair 21; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics*; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D015870:Gene Expression; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008969:Molecular Sequence Data; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D017931:DNA Primers; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014157:Transcription Factors