Abstract
We have previously demonstrated that translocations of VH genes from chromosome 14 to chromosome 8 and of the c-myc oncogene from chromosome 8 to chromosome 14 occur in Burkitt lymphomas with the t(8;14) chromosome translocation. An association of the c-myc gene with the Cμ immunoglobulin gene has been observed in some but not all Burkitt lymphomas studied previously. In the present study, we have investigated the organization of the human heavy chain locus and of the c-myc gene in the P3HR-1 Burkitt lymphoma cell line. Becuase mouse/P3HR-1 somatic cell hybrids that retain only the 14q+ chromosome and no other human chromosome contain the human Cμ and Cγ genes but not VH genes, we have concluded that the breakpoint on chromosome 14 in P3HR-1 cells is distal to Cμ and between Cμ and VH. Thus, the breakpoint of human chromosome 14 differs in different Burkitt lymphoma cell lines. We also found that the human c-myc oncogene translocated to chromosome 14 in the P3HR-1 cell line is not recombined with the Cμ gene. The breakpoint on human chromosome 8 may therefore also differ in different Burkitt lymphoma cell lines, because we have observed DNA rearrangement of the c-myc gene with the Cμ gene in only some of the Burkitt lymphoma cell lines studied elsewhere. Interestingly, high levels of transcripts of the c-myc oncogene were observed in Burkitt lymphomas with translocated c-myc oncogenes both rearranged and unrearranged. Therefore, the translocation of a c-myc oncogene to the heavy chain locus on human chromosome 14 is apparently sufficient for its transcriptional activation and may be an essential step in the pathway leading to neoplasia.
Keywords: chromosome translocations, oncogene activation, human B cell neoplasia
Full text
PDF




Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Alexander A., Steinmetz M., Barritault D., Frangione B., Franklin E. C., Hood L., Buxbaum J. N. gamma Heavy chain disease in man: cDNA sequence supports partial gene deletion model. Proc Natl Acad Sci U S A. 1982 May;79(10):3260–3264. doi: 10.1073/pnas.79.10.3260. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ar-Rushdi A., Tan K. B., Croce C. M. Transcriptional control of the expression of mouse globin genes in myeloma x erythroleukemia cell hybrids. Somatic Cell Genet. 1982 Mar;8(2):151–161. doi: 10.1007/BF01538674. [DOI] [PubMed] [Google Scholar]
- Benjamin D., Magrath I. T., Maguire R., Janus C., Todd H. D., Parsons R. G. Immunoglobulin secretion by cell lines derived from African and American undifferentiated lymphomas of Burkitt's and non-Burkitt's type. J Immunol. 1982 Sep;129(3):1336–1342. [PubMed] [Google Scholar]
- Bernheim A., Berger R., Lenoir G. Cytogenetic studies on African Burkitt's lymphoma cell lines: t(8;14), t(2;8) and t(8;22) translocations. Cancer Genet Cytogenet. 1981 Jun;3(4):307–315. doi: 10.1016/0165-4608(81)90039-x. [DOI] [PubMed] [Google Scholar]
- Bobrow M., Cross J. Differential staining of human and mouse chromosomes in interspecific cell hybrids. Nature. 1974 Sep 6;251(5470):77–79. doi: 10.1038/251077a0. [DOI] [PubMed] [Google Scholar]
- Croce C. M. Assignment of the integration site for simian virus 40 to chromosome 17 in GM54VA, a human cell line transformed by simian virus 40. Proc Natl Acad Sci U S A. 1977 Jan;74(1):315–318. doi: 10.1073/pnas.74.1.315. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Croce C. M., Shander M., Martinis J., Cicurel L., D'Ancona G. G., Dolby T. W., Koprowski H. Chromosomal location of the genes for human immunoglobulin heavy chains. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3416–3419. doi: 10.1073/pnas.76.7.3416. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dalla-Favera R., Bregni M., Erikson J., Patterson D., Gallo R. C., Croce C. M. 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 Dec;79(24):7824–7827. doi: 10.1073/pnas.79.24.7824. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dalla-Favera R., Gelmann E. P., Martinotti S., Franchini G., Papas T. S., Gallo R. C., Wong-Staal F. Cloning and characterization of different human sequences related to the onc gene (v-myc) of avian myelocytomatosis virus (MC29). Proc Natl Acad Sci U S A. 1982 Nov;79(21):6497–6501. doi: 10.1073/pnas.79.21.6497. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dolby T. W., Devuono J., Croce C. M. Cloning and partial nucleotide sequence of human immunoglobulin mu chain cDNA from B cells and mouse-human hybridomas. Proc Natl Acad Sci U S A. 1980 Oct;77(10):6027–6031. doi: 10.1073/pnas.77.10.6027. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Erikson J., Croce C. M. Secretion of human immunoglobulins by mouse myeloma x Daudi somatic cell hybrids. Eur J Immunol. 1982 Aug;12(8):697–701. doi: 10.1002/eji.1830120814. [DOI] [PubMed] [Google Scholar]
- Erikson J., Finan J., Nowell P. C., Croce C. M. Translocation of immunoglobulin VH genes in Burkitt lymphoma. Proc Natl Acad Sci U S A. 1982 Sep;79(18):5611–5615. doi: 10.1073/pnas.79.18.5611. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Erikson J., Martinis J., Croce C. M. Assignment of the genes for human lambda immunoglobulin chains to chromosome 22. Nature. 1981 Nov 12;294(5837):173–175. doi: 10.1038/294173a0. [DOI] [PubMed] [Google Scholar]
- Glaser R., Nonoyama M., Hampar B., Croce C. M. Studies on the association of the Epstein-Barr virus genome and human chromosomes. J Cell Physiol. 1978 Sep;96(3):319–325. doi: 10.1002/jcp.1040960307. [DOI] [PubMed] [Google Scholar]
- Harris L. J., D'Eustachio P., Ruddle F. H., Marcu K. B. DNA sequence associated with chromosome translocations in mouse plasmacytomas. Proc Natl Acad Sci U S A. 1982 Nov;79(21):6622–6626. doi: 10.1073/pnas.79.21.6622. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hobart M. J., Rabbitts T. H., Goodfellow P. N., Solomon E., Chambers S., Spurr N., Povey S. Immunoglobulin heavy chain genes in humans are located on chromosome. Ann Hum Genet. 1981 Oct;45(Pt 4):331–335. doi: 10.1111/j.1469-1809.1981.tb00346.x. [DOI] [PubMed] [Google Scholar]
- Human gene mapping 6. Oslo conference (1981): Sixth International Workshop on Human Gene Mapping. Cytogenet Cell Genet. 1982;32(1-4):1–341. doi: 10.1159/000131680. [DOI] [PubMed] [Google Scholar]
- Kirsch I. R., Morton C. C., Nakahara K., Leder P. Human immunoglobulin heavy chain genes map to a region of translocations in malignant B lymphocytes. Science. 1982 Apr 16;216(4543):301–303. doi: 10.1126/science.6801764. [DOI] [PubMed] [Google Scholar]
- LITTLEFIELD J. W. SELECTION OF HYBRIDS FROM MATINGS OF FIBROBLASTS IN VITRO AND THEIR PRESUMED RECOMBINANTS. Science. 1964 Aug 14;145(3633):709–710. doi: 10.1126/science.145.3633.709. [DOI] [PubMed] [Google Scholar]
- Lenoir G. M., Preud'homme J. L., Bernheim A., Berger R. Correlation between immunoglobulin light chain expression and variant translocation in Burkitt's lymphoma. Nature. 1982 Jul 29;298(5873):474–476. doi: 10.1038/298474a0. [DOI] [PubMed] [Google Scholar]
- Linnenbach A., Huebner K., Croce C. M. Transcription of the simian virus 40 genome in DNA-transformed murine teratocarcinoma stem cells. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6386–6390. doi: 10.1073/pnas.78.10.6386. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Malcolm S., Barton P., Murphy C., Ferguson-Smith M. A., Bentley D. L., Rabbitts T. H. Localization of human immunoglobulin kappa light chain variable region genes to the short arm of chromosome 2 by in situ hybridization. Proc Natl Acad Sci U S A. 1982 Aug;79(16):4957–4961. doi: 10.1073/pnas.79.16.4957. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Manolov G., Manolova Y. Marker band in one chromosome 14 from Burkitt lymphomas. Nature. 1972 May 5;237(5349):33–34. doi: 10.1038/237033a0. [DOI] [PubMed] [Google Scholar]
- Marcu K. B., Harris L. J., Stanton L. W., Erikson J., Watt R., Croce C. M. Transcriptionally active c-myc oncogene is contained within NIARD, a DNA sequence associated with chromosome translocations in B-cell neoplasia. Proc Natl Acad Sci U S A. 1983 Jan;80(2):519–523. doi: 10.1073/pnas.80.2.519. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miyoshi I., Hiraki S., Kimura I., Miyamoto K., Sato J. 2/8 translocation in a Japanese Burkitt's lymphoma. Experientia. 1979 Jun 15;35(6):742–743. doi: 10.1007/BF01968217. [DOI] [PubMed] [Google Scholar]
- Ohno S., Babonits M., Wiener F., Spira J., Klein G., Potter M. Nonrandom chromosome changes involving the Ig gene-carrying chromosomes 12 and 6 in pristane-induced mouse plasmacytomas. Cell. 1979 Dec;18(4):1001–1007. doi: 10.1016/0092-8674(79)90212-5. [DOI] [PubMed] [Google Scholar]
- Seabright M. A rapid banding technique for human chromosomes. Lancet. 1971 Oct 30;2(7731):971–972. doi: 10.1016/s0140-6736(71)90287-x. [DOI] [PubMed] [Google Scholar]
- Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
- Taub R., Kirsch I., Morton C., Lenoir G., Swan D., Tronick S., Aaronson S., Leder P. 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 Dec;79(24):7837–7841. doi: 10.1073/pnas.79.24.7837. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Valbuena O., Marcu K. B., Croce C. M., Huebner K., Weigert M., Perry R. P. Chromosomal locations of mouse immunoglobulin genes. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2883–2887. doi: 10.1073/pnas.75.6.2883. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zech L., Haglund U., Nilsson K., Klein G. Characteristic chromosomal abnormalities in biopsies and lymphoid-cell lines from patients with Burkitt and non-Burkitt lymphomas. Int J Cancer. 1976 Jan 15;17(1):47–56. doi: 10.1002/ijc.2910170108. [DOI] [PubMed] [Google Scholar]