Abstract
A chromosomal translocation (Tx) that interrupts the transcription of either c-Myc or Pvt 1 is the principal lesion in many B cell malignancies including Burkitt’s Lymphoma (BL), AIDs-NHL, mouse plasmacytoma (Pct) and possibly multiple myeloma (MM). There is a restriction associated with this Tx such that only the immunoglobulin (Ig) heavy chain gene is found juxtaposed to c-Myc and only the Ig light chain gene is found juxtaposed to Pvt 1. Over the past several years, our laboratory has been instrumental in the elucidation of the structure of the mouse Pvt 1 locus as a means of understanding the relationship between these two divergent Txs which, nevertheless, produce indistinguishable disease phenotypes. In the mouse, we have identified a uniform Pvt1/Ig Ck fusion product which is consistently found in all tumors harboring Pvt 1 associated Txs. We have recently constructed transgenic mice harboring a translocated Pvt 1/Ck segment in order to determine whether 1). these mice produce the Pvt 1/Ck fusion product 2). these mice are immunocompromised and 3). these mice develop tumors of a B cell origin.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Erickson J, Nishikura K, Ar-Rushdi A, Finan J, Emmanuel B, Lenoir G, Nowell P and Croce C (1983) Translocation of an immunoglobulin k locus to a region 3′ of an unrearranged c-myc oncogene enhances c-myc transcription. Proc Natl Acad Sci USA 80: 7581–7585
Webb E, Adams JM and Cory S (1984) Variant (6;15) translocation in a murine plasmacytoma occurs near an immunoglobulin k gene but far from the myc oncogene. Nature 312:777–779
Graham M and Adams JM (1986) Chromosome 8 breakpoint far 3’ of the c-myc oncogene in a Burkitt’s lymphoma 2:8 variant translocation is equivalent to the murine pvt-1 locus. EMBO J 5: 2845–2851
Villeneuve L, Rassart E, Jolicoeur P, Graham M and Adams JM (1986) Proviral integration site Mis-1 in rat thymomas corresponds to the pvt-1 translocation breakpoint in murine plasmacytomas. Mol and Cell Biol 6:1834–1837
Cory S, Graham M, Webb E, Corcoran I and Adams JM (1985) Variant (6; 15) translocations in murine plasmacytomas involve a chromosome 15 locus at least 72kb from the c-myc oncogene. EMBO J 4:675–681
Tsichlis PN, Lee JS, Bear S, Lazo PA, Patriotis C, Gustafson E, Shinton S, Jenkins NA, Copeland NG, Huebner K, Croce C, Levan G and Hanson C (1989) Activation of multiple genes by provirus integration in the Mlvi-4 locus in T-cell lymphomas induced by moloney murine leukemia virus. J Virol. 64: 2236–2244
Kirsch IR, Brown JA, Lawrence J, Korsmeyer SJ and Norton CC (1985) Translocations that highlight chromosomal regions of differentiated activity. Cancer Genet Cytogenet 18:159–171
Huppi K, Siwarski D, Skurla R, Klinman D and Mushinski J F (1990) Pvt-1 transcripts are found in normal tissues and are altered by reciprocal (6;15) translocations in mouse plasmacytomas. Proc Natl Acad Sci USA 87: 6964–6968
Shtivelman E, Henglein B, Groitl P, Lipp M and Bishop JM (1989) Identification of a human transcription unit affected by the variant chromosomal translocations 2;8 and 8;22 of Burkitt lymphoma. Proc Natl Acad Sci USA 86: 3257–3260
Huppi K, Siwarski D, Goodnight J, Skurla Jr RM and Mushinski JF (1992) Alternative splicing of Pvt-1 transcripts in murine B-lymphocytic neoplasms accompanies amplification and chromosomal translocation. Int J of Oncol 1:525–532
Huppi K and Siwarski D (1994) Chimeric transcripts with an open reading frame are generated as a result of translocation to the Pvt-1 region in mouse B-cell tumors. Int J Cancer 59:848–851
Axelson H, Panda CK, Silva S, Sugiyama H, Wiener F, Klein G and Sumegi J (1991) A new variant 15; 16 translocation in mouse plasmacytoma leads to the juxtaposition of c-myc and immunoglobulin lambda. Oncogene 6: 2263–2270
Karasuyama H, Rolink A, Shinkai Y, Young F, Alt FW and Melchers F (1994) The expression of Vpre-B/15 surrogate light chain in early bone marrow precursor B cells of normal and B cell-deficient mutant mice. Cell 77:133–143
Shtivelman E and Bishop JM (1990) Effects of Translocations on Transcription from PVT. Mol and Cell Biol 10:1835–1839
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1997 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Siwarski, D. et al. (1997). Structure and Expression of the c-Myc/Pvt 1 Megagene Locus. In: Potter, M., Melchers, F. (eds) C-Myc in B-Cell Neoplasia. Current Topics in Microbiology and Immunology, vol 224. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-60801-8_6
Download citation
DOI: https://doi.org/10.1007/978-3-642-60801-8_6
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-64560-0
Online ISBN: 978-3-642-60801-8
eBook Packages: Springer Book Archive