Identification of novel fusion genes with 28S ribosomal DNA in hematologic malignancies

Kobayashi,Satoru; Taki,Tomohiko; Nagoshi,Hisao; Chinen,Yoshiaki; Yokokawa,Yuichi; Kanegane,Hirokazu; Matsumoto,Yosuke; Kuroda,Junya; Horiike,Shigeo; Nishida,Kazuhiro; Taniwaki,Masafumi

doi:10.3892/ijo.2014.2291

2014-April Volume 44 Issue 4

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2014-April Volume 44 Issue 4

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Article

Identification of novel fusion genes with 28S ribosomal DNA in hematologic malignancies

Authors:
- Satoru Kobayashi
- Tomohiko Taki
- Hisao Nagoshi
- Yoshiaki Chinen
- Yuichi Yokokawa
- Hirokazu Kanegane
- Yosuke Matsumoto
- Junya Kuroda
- Shigeo Horiike
- Kazuhiro Nishida
- Masafumi Taniwaki
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Affiliations: Department of Molecular Hematology and Oncology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan, Department of Molecular Diagnostics and Therapeutics, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan, Department of Pediatrics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan
Pages: 1193-1198
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Published online on: February 5, 2014

https://doi.org/10.3892/ijo.2014.2291
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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.

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1.	Taki T and Taniwaki M: Chromosomal translocations in cancer and their relevance for therapy. Curr Opin Oncol. 18:62–68. 2006. View Article : Google Scholar : PubMed/NCBI
2.	Tomlins SA, Rhodes DR, Perner S, et al: Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science. 310:644–648. 2005. View Article : Google Scholar : PubMed/NCBI
3.	Euhus DM, Timmons CF and Tomlinson GE: ETV6-NTRK3 - Trk-ing the primary event in human secretory breast cancer. Cancer Cell. 2:347–348. 2002. View Article : Google Scholar : PubMed/NCBI
4.	Soda M, Choi YL, Enomoto M, et al: Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 448:561–566. 2007. View Article : Google Scholar : PubMed/NCBI
5.	Kobayashi S, Taki T, Chinen Y, et al: Identification of IGHC5-BACH2 fusion transcripts resulting from cryptic chromosomal rearrangements of 14q32 with 6q15 in aggressive B-cell lymphoma/leukemia. Genes Chromosomes Cancer. 50:207–216. 2011.
6.	Chesi M, Nardini E, Lim RS, Smith KD, Kuehl WM and Bergsagel PL: The t(4;14) translocation in myeloma dysregulates both FGFR3 and a novel gene, MMSET, resulting in IgH/MMSET hybrid transcripts. Blood. 92:3025–3034. 1998.PubMed/NCBI
7.	Hatzivassiliou G, Miller I, Takizawa J, et al: IRTA1 and IRTA2, novel immunoglobulin superfamily receptors expressed in B cells and involved in chromosome 1q21 abnormalities in B cell malignancy. Immunity. 14:277–289. 2001. View Article : Google Scholar
8.	Przybylski GK, Dik WA, Wanzeck J, et al: Disruption of the BCL11B gene through inv(14)(q11.2q32.31) results in the expression of BCL11B-TRDC fusion transcripts and is associated with the absence of wild-type BCL11B transcripts in T-ALL. Leukemia. 19:201–208. 2005. View Article : Google Scholar : PubMed/NCBI
9.	Nagoshi H, Taki T, Hanamura I, et al: Frequent PVT1 rearrangement and novel chimeric genes PVT1-NBEA and PVT1-WWOX occur in multiple myeloma with 8q24 abnormality. Cancer Res. 72:4954–4962. 2012. View Article : Google Scholar : PubMed/NCBI
10.	Pleasance ED, Stephens PJ, O’Meara S, et al: A small-cell lung cancer genome with complex signatures of tobacco exposure. Nature. 463:184–190. 2010. View Article : Google Scholar : PubMed/NCBI
11.	Northcott PA, Shih DJ, Peacock J, et al: Subgroup-specific structural variation across 1,000 medulloblastoma genomes. Nature. 488:49–56. 2012. View Article : Google Scholar
12.	Chinen Y, Taki T, Nishida K, et al: Identification of the novel AML1 fusion partner gene, LAF4, a fusion partner of MLL, in childhood T-cell acute lymphoblastic leukemia with t(2;21) (q11;q22) by bubble PCR method for cDNA. Oncogene. 27:2249–2256. 2008. View Article : Google Scholar : PubMed/NCBI
13.	Chen YW, Hu XT, Liang AC, et al: High BCL6 expression predicts better prognosis, independent of BCL6 translocation status, translocation partner, or BCL6-deregulating mutations, in gastric lymphoma. Blood. 108:2373–2383. 2006. View Article : Google Scholar
14.	Montanaro L, Treré D and Derenzini M: Changes in ribosome biogenesis may induce cancer by down-regulating the cell tumor suppressor potential. Biochim Biophys Acta. 1825:101–110. 2012.PubMed/NCBI
15.	Dai MS and Lu H: Crosstalk between c-Myc and ribosome in ribosomal biogenesis and cancer. J Cell Biochem. 105:670–677. 2008. View Article : Google Scholar : PubMed/NCBI
16.	Li Z and Hann SR: Nucleophosmin is essential for c-Myc nucleolar localization and c-Myc-mediated rDNA transcription. Oncogene. 32:1988–1994. 2013. View Article : Google Scholar
17.	Grandori C, Gomez-Roman N, Felton-Edkins ZA, et al: c-Myc binds to human ribosomal DNA and stimulates transcription of rRNA genes by RNA polymerase I. Nat Cell Biol. 7:311–318. 2005. View Article : Google Scholar : PubMed/NCBI
18.	Stults DM, Killen MW, Williamson EP, et al: Human rRNA gene clusters are recombinational hotspots in cancer. Cancer Res. 69:9096–10104. 2009. View Article : Google Scholar : PubMed/NCBI
19.	Uemura M, Zheng Q, Koh CM, Nelson WG, Yegnasubramanian S and De Marzo AM: Overexpression of ribosomal RNA in prostate cancer is common but not linked to rDNA promoter hypomethylation. Oncogene. 31:1254–1263. 2012. View Article : Google Scholar : PubMed/NCBI
20.	Croce CM and Nowell PC: Molecular basis of human B cell neoplasia. Blood. 65:1–7. 1985.
21.	MacLeod RA, Nagel S, Kaufmann M, Janssen JW and Drexler HG: Activation of HOX11L2 by juxtaposition with 3’-BCL11B in an acute lymphoblastic leukemia cell line (HPB-ALL) with t(5;14) (q35;q32.2). Genes Chromosomes Cancer. 37:84–91. 2003.PubMed/NCBI
22.	Fujimoto R, Ozawa T, Itoyama T, Sadamori N, Kurosawa N and Isobe M: HELIOS-BCL11B fusion gene involvement in a t(2;14) (q34;q32) in an adult T-cell leukemia patient. Cancer Genet. 205:356–364. 2012. View Article : Google Scholar : PubMed/NCBI
23.	Ungar D, Oka T, Brittle EE, et al: Characterization of a mammalian Golgi-localized protein complex, COG, that is required for normal Golgi morphology and function. J Cell Biol. 157:405–415. 2002. View Article : Google Scholar : PubMed/NCBI
24.	Velagaleti GV, Tonk VS, Hakim NM, et al: Fusion of HMGA2 to COG5 in uterine leiomyoma. Cancer Genet Cytogenet. 202:11–16. 2010. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Identification of novel fusion genes with 28S ribosomal DNA in hematologic malignancies

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