title: Identification of a novel fusion gene, TTL, fused to ETV6 in acute lymphoblastic leukemia with t(12;13)(p13;q14), and its implication in leukemogenesis.
abstract: ETS variant gene 6 (ETV6)/translocation, ETS, leukemia (TEL)-involving chromosomal translocations are frequently observed in various hematologic neoplasms. We describe here a novel ETV6-involving translocation, t(12;13)(p13;q14), found in the case of acute lymphoblastic leukemia, in which ETV6 fused with a previously unknown gene, named Twelve-thirteen Translocation Leukemia gene (TTL), at 13q14. TTL was weakly but ubiquitously expressed in normal human tissues as detected by reverse transcribed-PCR. Three TTL splicing forms were identified, TTL-T from a human testis cDNA library, with an open-reading frame of 402 bp encoding 133 amino acids (aa), and TTL-B1 and -B2 from a human brain cDNA library. These proteins have no homology to known proteins. In leukemic cells from the patient, both reciprocal fusion transcripts, ETV6/TTL and TTL/ETV6, were expressed. The predominant fusion transcript, TTL/ETV6-1, encodes a predicted 530 aa fusion protein containing 89 aa of the N-terminal TTL fusing to the helix-loop-helix domain and ETS-binding domain of ETV6. Although the function of TTL is yet to be elucidated, our findings will provide another insight into the molecular pathogenesis of leukemia having ETV6-involving translocations.
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Qiao
authors.forename: S
authors.initials: S
authors.lastname: Ogawa
authors.forename: A
authors.initials: A
authors.lastname: Hangaishi
authors.forename: K
authors.initials: K
authors.lastname: Yuji
authors.forename: K
authors.initials: K
authors.lastname: Izutsu
authors.forename: A
authors.initials: A
authors.lastname: Kunisato
authors.forename: Y
authors.initials: Y
authors.lastname: Imai
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: N
authors.initials: N
authors.lastname: Hosoya
authors.forename: Y
authors.initials: Y
authors.lastname: Nannya
authors.forename: Y
authors.initials: Y
authors.lastname: Sato
authors.forename: K
authors.initials: K
authors.lastname: Maki
authors.forename: K
authors.initials: K
authors.lastname: Mitani
authors.forename: H
authors.initials: H
authors.lastname: Hirai
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D015139:Blotting, Southern; D001921:Brain; D002881:Chromosomes, Human, Pair 12; D002882:Chromosomes, Human, Pair 13; D003001:Cloning, Molecular; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015723:Gene Library; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D020033:Protein Isoforms; D050783:Proto-Oncogene Proteins c-ets; D012334:RNA, Neoplasm / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D012097:Repressor Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013737:Testis; D014178:Translocation, Genetic; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; D015514:Oncogene Proteins, Fusion; D020033:Protein Isoforms; D050783:Proto-Oncogene Proteins c-ets; D012334:RNA, Neoplasm; D012097:Repressor Proteins; D000097764:ETS Translocation Variant 6 Protein; C475279:TTL-ETV6 fusion protein, human