title: TEL gene is involved in myelodysplastic syndromes with either the typical t(5;12)(q33;p13) translocation or its variant t(10;12)(q24;p13).
abstract: A t(5;12)(q33;p13) translocation is a recurrent chromosome abnormality in a subgroup of myeloid malignancies with features of both myeloproliferative disorders and myelodysplastic syndromes (MDSs). The molecular consequence of a t(5;12) is a fusion between the platelet-derived growth factor receptor-B gene on chromosome 5 and a novel ETS-like gene, TEL, on chromosome 12. We report on three patients with a t(5;12)(q33;p13) diagnosed as chronic myelomonocytic leukemia, and one case of a t(10;12)(q24;p13) in a progressive MDS, with eosinophilia and monocytosis. Involvement of the TEL gene in these chromosome translocations was investigated by fluorescence in situ hybridization (FISH) with cosmid probes containing selectively the 5' end or 3' end of TEL. Hybridization of these cosmids to the der(5)/der(10) or a der(12), respectively, demonstrated a rearrangement of TEL in both translocations, showing that the t(10;12) is a variant translocation of the t(5;12). Cloning of the fusion cDNA of one case of t(5;12) showed that the breakpoint occurred at the RNA level at exactly the same position as reported by Golub et al (Cell 77:307, 1994). In addition, the TEL gene on chromosome 12 could be localized between two probes previously mapped to 12p13, namely PRB1 and D12S178, leading to a better definition of the position of TEL in this chromosome region. Moreover, in the case involving chromosome 10, the breakpoint occurred between cKTN206 and cKTN312/LYT-10 at 10q24. Clinicohematological data in these studies as well as the restriction mapping of chromosomal breakpoints strongly suggest that (1) common features in MDSs involving the TEL gene are monocytosis and eosinophilia, (2) chromosomes other than no. 5 may be involved and at least a t(10;12)(q24;p13) variant chromosome translocation does exist in these MDSs, and (3) both standard and variant 12p/TEL translocations may be identified by FISH with appropriate probes.
authors.affiliation: Center for Human Genetics, University of Leuven, Belgium.
authors.forename: I
authors.initials: I
authors.lastname: Wlodarska
authors.forename: C
authors.initials: C
authors.lastname: Mecucci
authors.forename: P
authors.initials: P
authors.lastname: Marynen
authors.forename: C
authors.initials: C
authors.lastname: Guo
authors.forename: D
authors.initials: D
authors.lastname: Franckx
authors.forename: R
authors.initials: R
authors.lastname: La Starza
authors.forename: A
authors.initials: A
authors.lastname: Aventin
authors.forename: A
authors.initials: A
authors.lastname: Bosly
authors.forename: M F
authors.initials: MF
authors.lastname: Martelli
authors.forename: J J
authors.initials: JJ
authors.lastname: Cassiman
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D002869:Chromosome Aberrations / Q000235:genetics; D025063:Chromosome Disorders; D002879:Chromosomes, Human, Pair 10; D002881:Chromosomes, Human, Pair 12; D002895:Chromosomes, Human, Pair 5; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015477:Leukemia, Myelomonocytic, Chronic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D050783:Proto-Oncogene Proteins c-ets; D012334:RNA, Neoplasm / Q000235:genetics; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics; D012097:Repressor Proteins; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D017931:DNA Primers; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D050783:Proto-Oncogene Proteins c-ets; D012334:RNA, Neoplasm; D017479:Receptors, Platelet-Derived Growth Factor; D012097:Repressor Proteins; D014157:Transcription Factors; D000097764:ETS Translocation Variant 6 Protein