Skip to main content

Advertisement

SpringerLink
Log in

Recurrent intragenic exon rearrangements of SOBP and AUTS2 in non-Hodgkin B-cell lymphoma

  • Original Article
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

Expression of intragenic exon rearrangements (IERs) has reportedly been detected in both normal and cancer cells. However, there have been few reports of occurrence of these rearrangements specific to neoplasms including malignant lymphoma. In this study, we detected IERs of ten genes (NBPF8, SOBP, AUTS2, RAB21, SPATA13, ABCC4, WDR7, PHLPP1, NFATC1 and MAGED1) in non-Hodgkin B cell lymphoma (B-NHL) cell line KPUM-UH1 using a high-resolution single nucleotide polymorphism array and reverse transcription polymerase chain reaction using reversely directed divergent primers within exons involved in genomic intragenic gains followed by sequencing analysis. Among them, the IERs involved in SOBP (6q21) exon 2 and 3 and AUTS2 (7q11.22) exon 2–4 were the molecular lesions specific to tumors and were frequently detected in B-NHL samples. These IERs constitute novel genetic alterations of B-NHL, which might be associated with tumorigenesis and be useful as genetic biological markers.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Dalla-Favera R, Bregni M, Erikson J, Patterson D, Gallo RC, Croce CM. Human c-myc onc gene is located on the region of chromosome 8 that is translocated in Burkitt lymphoma cells. Proc Natl Acad Sci U S A. 1982;79:7824–7.

    Article  CAS  Google Scholar 

  2. Taub R, Kirsch I, Morton C, Lenoir G, Swan D, Tronick S, et al. Translocation of the c-myc gene into the immunoglobulin heavy chain locus in human Burkitt lymphoma and murine plasmacytoma cells. Proc Natl Acad Sci U S A. 1982;79:7837–41.

    Article  CAS  Google Scholar 

  3. Taniwaki M, Nishida K, Ueda Y, Misawa S, Nagai M, Tagawa S, et al. Interphase and metaphase detection of the breakpoint of 14q32 translocations in B cell malignancies by double-color fluorescence in situ hybridization. Blood. 1995;85:3223–8.

    Article  CAS  Google Scholar 

  4. Taniwaki M, Sliverman GA, Nishida K, Horiike S, Misawa S, Shimazaki C, et al. Translocations and amplification of the BCL2 gene are detected in interphase nuclei of non-Hodgkin’s lymphoma by in situ hybridization with yeast artificial chromosome clones. Blood. 1995;86:1481–6.

    Article  CAS  Google Scholar 

  5. Davis RE, Ngo VN, Lenz G, Tolar P, Young RM, Romesser PB, et al. Chronic active B cell-receptor signalling in diffuse large B cell lymphoma. Nature. 2010;463:88–92.

    Article  CAS  Google Scholar 

  6. Lenz G, Davis RE, Ngo VN, Lam L, George TC, Wright GW, et al. Oncogenic CARD11 mutations in human diffuse large B cell lymphoma. Science. 2008;319:1676–9.

    Article  CAS  Google Scholar 

  7. Ngo VN, Young RM, Schmitz R, Jhavar S, Xiao W, Lim KH, et al. Oncogenically active MYD88 mutations in human lymphoma. Nature. 2011;470:115–9.

    Article  CAS  Google Scholar 

  8. Kato M, Sanada M, Kato I, Sato Y, Takita J, Takeuchi K, et al. Frequent inactivation of A20 in B cell lymphomas. Nature. 2009;459:712–6.

    Article  CAS  Google Scholar 

  9. Compagno M, Lim WK, Grunn A, Nandula SV, Brahmachary M, Shen Q, et al. Mutations of multiple genes cause deregulation of NF-κB in diffuse large B cell lymphoma. Nature. 2009;459:717–21.

    Article  CAS  Google Scholar 

  10. Nakao M, Yokota S, Iwai T, Kaneko H, Horiike S, Kashima K, et al. Internal tandem duplication of the flt3 gene found in acute myeloid leukemia. Leukemia. 1996;10:1911–8.

    CAS  PubMed  Google Scholar 

  11. Yu M, Honoki K, Andersen J, Paietta E, Nam DK, Yunis JJ. MLL tandem duplication and multiple splicing in adult acute myeloid leukemia with normal karyotype. Leukemia. 1996;10:774–80.

    CAS  PubMed  Google Scholar 

  12. Fenstermaker RA, Ciesielski MJ, Castiglia GJ. Tandem duplication of the epidermal growth factor receptor tyrosine kinase and calcium internalization domains in A-172 glioma cells. Oncogene. 1998;16:3435–43.

    Article  CAS  Google Scholar 

  13. Salzman J, Gawad C, Wang PL, Lacayo N, Brown PO. Circular RNAs are the predominant transcript isoform from hundreds of human genes in diverse cell types. PLoS One. 2012;7:e30733.

    Article  CAS  Google Scholar 

  14. Guarnerio J, Bezzi M, Jeong JC, Paffenholz SV, Berry K, Naldini MM, et al. Oncogenic role of fusion-circRNAs derived from cancer-associated chromosomal translocations. Cell. 2016;165:289–302.

    Article  CAS  Google Scholar 

  15. Sasaki N, Kuroda J, Nagoshi H, Yamamoto M, Kobayashi S, Tsutsumi Y, et al. Bcl-2 is a better therapeutic target than c-Myc, but attacking both could be a more effective treatment strategy for B cell lymphoma with concurrent Bcl-2 and c-Myc overexpression. Exp Hematol. 2011;39:817–28.

    Article  CAS  Google Scholar 

  16. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, et al. Initial sequencing and analysis of the human genome. Nature. 2001;409:860–921.

    Article  CAS  Google Scholar 

  17. Nannya Y, Sanada M, Nakazaki K, Hosoya N, Wang L, Hangaishi A, et al. A robust algorithm for copy number detection using high-density oligonucleotide single nucleotide polymorphism genotyping arrays. Cancer Res. 2005;65:6071–9.

    Article  CAS  Google Scholar 

  18. Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J, Rybak A, et al. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature. 2013;495:333–8.

    Article  CAS  Google Scholar 

  19. Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, et al. Natural RNA circles function as efficient microRNA sponges. Nature. 2013;495:384–8.

    Article  CAS  Google Scholar 

  20. Nagoshi H, Taki T, Hanamura I, Nitta M, Otsuki T, Nishida K, et al. Frequent PVT1 rearrangement and novel chimeric genes PVT1-NBEA and PVT1-WWOX occur in multiple myeloma with 8q24 abnormality. Cancer Res. 2012;72:4954–62.

    Article  CAS  Google Scholar 

  21. Chinen Y, Sakamoto N, Nagoshi H, Taki T, Maegawa S, Tatekawa S, et al. 8q24 amplified segments involve novel fusion genes between NSMCE2 and long noncoding RNAs in acute myelogenous leukemia. J Hematol Oncol. 2014;7:68.

    Article  Google Scholar 

  22. Birk E, Har-Zahav A, Manzini CM, Pasmanik-Chor M, Kornreich L, Walsh CA, et al. SOBP is mutated in syndromic and nonsyndromic intellectual disability and is highly expressed in the brain limbic system. Am J Hum Genet. 2010;87:694–700.

    Article  CAS  Google Scholar 

  23. Kawamata N, Ogawa S, Zimmermann M, Niebuhr B, Stocking C, Sanada M, et al. Cloning of genes involved in chromosomal translocations by high-resolution single nucleotide polymorphism genomic microarray. Proc Natl Acad Sci U S A. 2008;105:11921–6.

    Article  CAS  Google Scholar 

  24. Coyaud E, Struski S, Dastugue N, Brousset P, Broccardo C, Bradtke J. PAX5-AUTS2 fusion resulting from t(7;9)(q1.1 2;p1.3 2) can now be classified as recurrent in B cell acute lymphoblastic leukemia. Leuk Res. 2010;34:e323–5.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Hematology, Japanese Red Cross Kyoto Daiichi Hospital, 15-749, Honmachi, Higashiyama-ku, Kyoto, 605-8981, Japan

    Yosuke Matsumoto, Ayako Muramatsu, Kodai Kuriyama, Muneo Ohshiro, Yoshiko Hirakawa, Toshiki Iwai & Hitoji Uchiyama

  2. Department of Hematology, Fukuchiyama City Hospital, Fukuchiyama, Japan

    Yoshiaki Chinen

  3. Division of Hematology and Oncology, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Yoshiaki Chinen, Yuji Shimura, Shigeo Horiike & Junya Kuroda

  4. Department of Hematology and Oncology, Hiroshima University, Hiroshima, Japan

    Hisao Nagoshi

  5. Department of Hematology, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan

    Nana Sasaki

  6. Department of Medical Technology, Kyorin University, Faculty of Health Science, Tokyo, Japan

    Tomohiko Taki

  7. Center for Molecular Diagnostics and Therapeutics, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Tomohiko Taki & Masafumi Taniwaki

Authors
  1. Yosuke Matsumoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yoshiaki Chinen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yuji Shimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hisao Nagoshi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nana Sasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ayako Muramatsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kodai Kuriyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Muneo Ohshiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yoshiko Hirakawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Toshiki Iwai
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Hitoji Uchiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Tomohiko Taki
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Shigeo Horiike
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Junya Kuroda
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Masafumi Taniwaki
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yosuke Matsumoto.

Ethics declarations

Conflict of interest

The authors have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

12185_2019_2766_MOESM1_ESM.pptx

Supplementary Fig. 1: Sequencing analyses of eight genes with the IERs of KPUM-UH1. The IERs of NBPF8, ABCC4 and NFATC1 were in-frame. Supplementary Table 1: Cell lines and primary samples of various tumors analyzed in this study. Supplementary Table 2: Fifty-four genes with intragenic gains of the genomic DNA identified by means of high-density SNP genotyping arrays in KPUM-UH1. The amplified exons or introns are shown in parentheses. Ten genes shown in bold type were confirmed to have IERs by RT-PCR and subsequent sequencing analyses. Supplementary Table 3: The ten genes with the IERs detected in KPUM-UH1. Supplementary Table 4: The RDD primer sets of the ten genes with the IERs. Although RT-PCR was performed by using the RDD primer sets for 54 genes listed in Supplementary Table 2, the list of the primer sets of 44 genes are omitted. Supplementary Table 5: Primer sets for detection of the IERs of SOBP and AUTS2. The locations of these primers in SOBP and AUTS2 are shown in Figs. 3 and 4, respectively

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Matsumoto, Y., Chinen, Y., Shimura, Y. et al. Recurrent intragenic exon rearrangements of SOBP and AUTS2 in non-Hodgkin B-cell lymphoma. Int J Hematol 111, 75–83 (2020). https://doi.org/10.1007/s12185-019-02766-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-019-02766-z

Keywords

Search

Navigation