Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Oncogenomics
  • Published:

Large-scale identification of novel potential disease loci in mouse leukemia applying an improved strategy for cloning common virus integration sites

Oncogene volume 21, pages 7247–7255 (2002)Cite this article

Abstract

The identification of common virus integration sites (cVIS) in retrovirally induced tumors in mice provides a powerful strategy to isolate novel transforming genes. Applying virus LTR-specific inverse-PCR and RT–PCR combined with automated sequencing on CasBr-M Murine Leukemia Virus (MuLV) induced myeloid leukemias, 126 virus integration sites were cloned. Using locus- and LTR-specific primers, a nested-PCR/Southern-blotting procedure was developed on genomic DNA from a large panel of MuLV-induced leukemias, to analyse whether a particular virus insertion represented a cVIS. In fact 39 out of 41 integrations analysed this way appeared to represent a common virus integration. We recognized six previously cloned cVISs, i.e. Evi1, Hoxa7, c-Myb, Cb2/Evi11, Evi12, and His1 and 33 novel common insertions, designated Cas-Br Virus Integration Site (Casvis). Among this group we found integrations in or near genes encoding nuclear proteins, e.g. Dnmt-2, Nm23-M2, Ctbp1 or Erg, within receptor genes, e.g. Cb2 or mrc1, novel putative signaling or transporter genes, the ringfinger-protein gene Mid1 and a panel of genes encoding novel proteins with unknown function. The finding that 39 out of 41 integrations analysed represented a cVIS, suggests that the majority of the other virus insertions that were not yet analysed by the PCR/Southern-blotting method are located in a cVIS as well and may therefore also harbor novel disease genes.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  • Bergeron D, Poliquin L, Kozak CA, Rassart E . 1991 J. Virol. 65: 7–15

  • Berns A, Mikkers H, Krimpenfort P, Allen J, Scheijen B, Jonkers J . 1999 Cancer Res. 59: 1773s–1777s

  • Berns A, van der Lugt N, Alkema M, van Lohuizen M, Domen J, Acton D, Allen J, Laird PW, Jonkers J . 1994 Cold Spring Harb. Symp. Quant. Biol. 59: 435–447

  • Buchberg AM, Bedigian HG, Jenkins NA, Copeland NG . 1990 Mol. Cell. Biol. 10: 4658–4666

  • Cox MC, Panetta P, Venditti A, Abruzzese E, Del Poeta G, Cantonetti M, Amadori S . 2001 Leuk. Res. 25: 349–351

  • de Boer CJ, van Krieken JH, Schuuring E, Kluin PM . 1997 Ann. Oncol. 8: 109–117

  • Hansen GM, Skapura D, Justice MJ . 2000 Genome Res. 10: 237–243

  • Hirvonen H, Hukkanen V, Salmi TT, Pelliniemi TT, Alitalo R . 1993 Leuk. Lymphoma 11: 197–205

  • Holmes KL, Langdon WY, Fredrickson TN, Coffman RL, Hoffman PM, Hartley JW, Morse III HC . 1986 J. Immunol. 137: 679–688

  • Holmes KL, Palaszynski E, Fredrickson TN, Morse III HC, Ihle JN . 1985 Proc. Natl. Acad. Sci. USA 82: 6687–6691

  • Ihle JN, Rein A, Mural R . 1984 Viral Oncol. 4: 95–137

  • Joosten M, Valk PJ, Vankan Y, de Both N, Lowenberg B, Delwel R . 2000 Virology 268: 308–318

  • Li J, Shen H, Himmel KL, Dupuy AJ, Largaespada DA, Nakamura T, Shaughnessy Jr JD, Jenkins NA, Copeland NG . 1999 Nat. Genet. 23: 348–353

  • Morishita K, Parganas E, Bartholomew C, Sacchi N, Valentine MB, Raimondi SC, Le Beau MM, Ihle JN . 1990 Oncogene Res. 5: 221–231

  • Morishita K, Parker DS, Mucenski ML, Jenkins NA, Copeland NG, Ihle JN . 1988 Cell 54: 831–840

  • Nakamura T, Largaespada DA, Lee MP, Johnson LA, Ohyashiki K, Toyama K, Chen SJ, Willman CL, Chen IM, Feinberg AP, Jenkins NA, Copeland NG, Shaughnessy Jr JD . 1996a Nat. Genet. 12: 154–158

  • Nakamura T, Largaespada DA, Shaughnessy Jr JD, Jenkins NA, Copeland NG . 1996b Nat. Genet. 12: 149–153

  • Ofir R, Gopas J, Aflalo E, Weinstein Y . 1992 Leuk. Res. 16: 797–806

  • Quaderi NA, Schweiger S, Gaudenz K, Franco B, Rugarli EI, Berger W, Feldman GJ, Volta M, Andolfi G, Gilgenkrantz S, Marion RW, Hennekam RC, Opitz JM, Muenke M, Ropers HH, Ballabio A . 1997 Nat. Genet. 17: 285–291

  • Rabbitts TH . 1994 Nature 372: 143–149

  • Rowley JD . 1999 Semin. Hematol. 36: 59–72

  • Setoguchi M, Higuchi Y, Yoshida S, Nasu N, Miyazaki Y, Akizuki S, Yamamoto S . 1989 Mol. Cell. Biol. 9: 4515–4522

  • Shannon KM, O'Connell P, Martin GA, Paderanga D, Olson K, Dinndorf P, McCormick F . 1994 N. Engl. J. Med. 330: 597–601

  • Shimizu K, Ichikawa H, Tojo A, Kaneko Y, Maseki N, Hayashi Y, Ohira M, Asano S, Ohki M . 1993 Proc. Natl. Acad. Sci. USA 90: 10280–10284

  • Side LE, Emanuel PD, Taylor B, Franklin J, Thompson P, Castleberry RP, Shannon KM . 1998 Blood 92: 267–272

  • Silver J, Buckler CE . 1986 J. Virol. 60: 1156–1158

  • Silver J, Keerikatte V . 1989 J. Virol. 63: 1924–1928

  • Specchia G, Mestice A, Clelia Storlazzi T, Anelli L, Pannunzio A, Grazia Roberti M, Rocchi M, Liso V . 2001 Leuk. Res. 25: 501–507

  • Tanaka K, Eguchi M, Eguchi-Ishimae M, Hasegawa A, Ohgami A, Kikuchi M, Kyo T, Asaoku H, Dohy H, Kamada N . 2001 Cancer Genet. Cytogenet. 124: 27–35

  • Valk P, Verbakel S, Vankan Y, Hol S, Mancham S, Ploemacher R, Mayen A, Lowenberg B, Delwel R . 1997a Blood 90: 1448–1457

  • Valk PJ, Hol S, Vankan Y, Ihle JN, Askew D, Jenkins NA, Gilbert DJ, Copeland NG, de Both NJ, Lowenberg B, Delwel R . 1997b J. Virol. 71: 6796–6804

  • Valk PJ, Joosten M, Vankan Y, Lowenberg B, Delwel R . 1997c Nucleic Acids Res. 25: 4419–4421

  • Valk PJ, Vankan Y, Joosten M, Jenkins NA, Copeland NG, Lowenberg B, Delwel R . 1999 J. Virol. 73: 3595–3602

Download references

Acknowledgements

This work was supported by the Dutch Cancer Society ‘Koningin Wilhelmina Fonds’, The Netherlands Organization for Scientific Research NWO and the Royal Dutch Academy of Sciences KNAW. The authors wish to thank Egied Simons for preparation of the figure.

Author information

Authors and Affiliations

  1. The Institute of Hematology, Erasmus University Rotterdam, Dr. Molewaterplein 50, Rotterdam, 3015GE, The Netherlands

    Marieke Joosten, Yolanda Vankan-Berkhoudt, Marjolein Tas, Monja Lunghi, Yvonne Jenniskens, Peter JM Valk, Bob Löwenberg, Eric van den Akker & Ruud Delwel

  2. St. Jude Children's Research Hospital, Memphis, Tennessee, USA

    Evan Parganas

Authors
  1. Marieke Joosten
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yolanda Vankan-Berkhoudt
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marjolein Tas
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Monja Lunghi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yvonne Jenniskens
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Evan Parganas
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Peter JM Valk
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Bob Löwenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Eric van den Akker
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ruud Delwel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ruud Delwel.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Joosten, M., Vankan-Berkhoudt, Y., Tas, M. et al. Large-scale identification of novel potential disease loci in mouse leukemia applying an improved strategy for cloning common virus integration sites. Oncogene 21, 7247–7255 (2002). https://doi.org/10.1038/sj.onc.1205813

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1205813

Keywords

This article is cited by

Search

Advanced search

Quick links