title: A novel cryptic translocation t(12;17)(p13;p12-p13) in a secondary acute myeloid leukemia results in a fusion of the ETV6 gene and the antisense strand of the PER1 gene.
abstract: The ETV6 gene is a member of the ETS family of transcription factors and the main target of chromosomal rearrangements affecting chromosome band 12p13. To date, more than 15 fusion partners of ETV6 have been characterized at the molecular level. Most of these fusions encode chimeric proteins with oncogenic properties. However, some of the translocations do not produce a functional fusion protein, but may induce ectopic expression of oncogenes located close to the breakpoint. We herein report the characterization and cloning of a novel cryptic translocation, t(12;17)(p13;p12-p13), occurring in a patient with an acute myeloid leukemia evolving from a chronic myelomonocytic leukemia. Cytogenetic analysis suggested the presence of a deletion of the short arm of chromosome 12, del(12)(p13), in three of the five metaphase cells analyzed. However, fluorescence in situ hybridization (FISH) with the ETV6-specific cosmid clones 179A6, 50F4, 163E7, and 148B6 as well as probes hybridizing to the TP53 gene on 17p13 and the subtelomeric region of 17p revealed the presence of a translocation between 12p and 17p. By FISH, the breakpoints could be localized in intron 1 of ETV6 and centromeric to TP53. By 3' rapid amplification of cDNA ends-polymerase chain reaction (3' RACE-PCR), a fusion transcript between exon 1 of ETV6 and the antisense strand of PER1 (period homolog 1, Drosophila), a circadian clock gene, could be identified. This ETV6-PER1 (antisense PER1 strand) fusion transcript does not produce a fusion protein, and no other fusion transcripts could be detected. We hypothesize that in the absence of a fusion protein, the inactivation of PER1 or deregulation of a gene in the neighborhood of PER1 may contribute to the pathogenesis of leukemias with a t(12;17)(p13;p12-p13).
authors.affiliation: Department of Medicine, Division of Hematology and Oncology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Eva Maria
authors.initials: EM
authors.lastname: Murga Penas
authors.forename: Jan
authors.initials: J
authors.lastname: Cools
authors.forename: Petra
authors.initials: P
authors.lastname: Algenstaedt
authors.forename: Kristina
authors.initials: K
authors.lastname: Hinz
authors.forename: Doris
authors.initials: D
authors.lastname: Seeger
authors.forename: Philippe
authors.initials: P
authors.lastname: Schafhausen
authors.forename: Georgia
authors.initials: G
authors.lastname: Schilling
authors.forename: Peter
authors.initials: P
authors.lastname: Marynen
authors.forename: Dieter K
authors.initials: DK
authors.lastname: Hossfeld
authors.forename: Judith
authors.initials: J
authors.lastname: Dierlamm
mesh_terms: D000208:Acute Disease; D000368:Aged; D001483:Base Sequence / Q000235:genetics; D018797:Cell Cycle Proteins; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D016373:DNA, Antisense / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D007951:Leukemia, Myeloid / Q000209:etiology / Q000235:genetics*; D015477:Leukemia, Myelomonocytic, Chronic / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D016609:Neoplasms, Second Primary / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D056950:Period Circadian Proteins; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics*; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D018797:Cell Cycle Proteins; D016373:DNA, Antisense; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D056950:Period Circadian Proteins; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D000097764:ETS Translocation Variant 6 Protein; C539022:PER1 protein, human