title: Identification of novel fusion genes with 28S ribosomal DNA in hematologic malignancies.
abstract: Fusion genes are frequently observed in hematologic malignancies and soft tissue sarcomas, and are usually associated with chromosome abnormalities. Many of these fusion genes create in-frame fusion transcripts that result in the production of fusion proteins, and some of which aid tumorigenesis. These fusion proteins are often associated with disease phenotype and clinical outcome, and act as markers for minimal residual disease and indicators of therapeutic targets. Here, we identified the 28S ribosomal DNA (RN28S1) gene as a novel fusion partner of the B-cell leukemia/lymphoma 11B gene (BCL11B), the immunoglobulin κ variable 3-20 gene (IGKV3-20) and the component of oligomeric Golgi complex 1 gene (COG1) in hematologic malignancies. The RN28S1-BCL11B fusion transcript was identified in a case with mixed-lineage (T/myeloid) acute leukemia having t(6;14)(q25;q32) by cDNA bubble PCR using BCL11B primers; however, the gene fused to BCL11B on 14q32 was not on 6q25. IGKV3-20-RN28S1 and COG1-RN28S1 fusion transcripts were identified in the Burkitt lymphoma cell line HBL-5, and the multiple myeloma cell line KMS-18. RN28S1 would not translate, and the breakpoints in partner genes of RN28S1 were within the coding exons, suggesting that disruption of fusion partners by fusion to RN28S1 is the possible mechanism of tumorigenesis. Although further analysis is needed to elucidate the mechanism(s) through which these RN28S1-related fusions play roles in tumorigenesis, our findings provide important insights into the role of rDNA function in human genomic architecture and tumorigenesis.
authors: Department of Molecular Hematology and Oncology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan.
authors: Satoru
authors: S
authors: Kobayashi
authors: Department of Molecular Diagnostics and Therapeutics, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan.
authors: Tomohiko
authors: T
authors: Taki
authors: Department of Molecular Hematology and Oncology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan.
authors: Hisao
authors: H
authors: Nagoshi
authors: Department of Molecular Hematology and Oncology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan.
authors: Yoshiaki
authors: Y
authors: Chinen
authors: Department of Molecular Diagnostics and Therapeutics, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan.
authors: Yuichi
authors: Y
authors: Yokokawa
authors: Department of Pediatrics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors: Hirokazu
authors: H
authors: Kanegane
authors: Department of Molecular Hematology and Oncology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan.
authors: Yosuke
authors: Y
authors: Matsumoto
authors: Department of Molecular Hematology and Oncology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan.
authors: Junya
authors: J
authors: Kuroda
authors: Department of Molecular Hematology and Oncology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan.
authors: Shigeo
authors: S
authors: Horiike
authors: Department of Molecular Hematology and Oncology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan.
authors: Kazuhiro
authors: K
authors: Nishida
authors: Department of Molecular Hematology and Oncology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan.
authors: Masafumi
authors: M
authors: Taniwaki
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics; D000293:Adolescent; D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000235:genetics; D045744:Cell Line, Tumor; D004275:DNA, Ribosomal / Q000235:genetics*; D019337:Hematologic Neoplasms / Q000235:genetics*; D006801:Humans; D015456:Leukemia, Biphenotypic, Acute / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000235:genetics; D012339:RNA, Ribosomal, 28S / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics; D017422:Sequence Analysis, DNA; D014178:Translocation, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; C479740:BCL11B protein, human; C486489:COG1 protein, human; D004275:DNA, Ribosomal; D012339:RNA, Ribosomal, 28S; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins