Biallelic alterations of both ETV6 and CDKN1B genes in a t(12;21) childhood acute lymphoblastic leukemia case.
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.
Wlodarska
I
I
Center for Human Genetics, Flanders Interuniversity Institute for Biotechnology, Leuven, Belgium.
Baens
M
M
Peeters
P
P
Aerssens
J
J
Mecucci
C
C
Brock
P
P
Marynen
P
P
Van den Berghe
H
H
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
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D017931:DNA Primers; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014157:Transcription Factors