Abstract
Our laboratory has focused on defining, localizing, and understanding the mode of action of genes involved in fractionated x-irradiation (FXI) leukemia in susceptible and resistant mouse strains. We have described the genetic and molecular evidence suggesting the existence of multiple independent loci involved in FXI-induced leukemogenesis. These studies indicated that one of these, Ril-1, a locus on the distal portion of chromosome 15, is the major locus influencing susceptibility to the disease. Our data unequivocally place Ril-1 in the gene complex Ly-6--Ril-1--Sis--H-30--Pol-5. Ril-1 appears to be closest to Ly-6 and Sis. We report that in FXI-induced leukemias there are hypomethylation changes in the Ly-6 region as compared to normal thymocytes. In contrast, Sis was found to be hypermethylated and not expressed. In addition, we have noted DNA rearrangements in the Ly-6--Pol-5 region in the majority of tumors examined using the Ly-6 and spleen focus-forming virus (SFFLV) molecular probes. Increased expression of Ly-6 and other surface markers encoded in this region has been noted in FXI-induced thymomas.
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Amari, N. M. B. and Meruelo, D.: Murine thymomas induced by fractionated-X-irradiation have specific T-cell receptor rearrangements and characteristics associated with day-15 to -16 fetal thymocytes. Mol Cell Biol 7: 4159–4168, 1987
Blin, N. and Stafford, D. W.: Isolation of high molecular weight DNA. Nucleic Acids Res 3: 2303–2308, 1976
Boehm, T. L. J. and Drahovsky, D.: Two-dimensional restriction mapping by digestion with restriction endonucleases of DNA in agarose and polyacrylamide gels. J Biochem Biophys Methods 9: 153–161, 1984
Cedar, H.: DNA methylation and gene activity. Cell 53: 3–4, 1988
Chandler, L. A., Ghazi, H., Jones, P. A., Boukamp, P., and Fusenig, N. E.: Allele-specific methylation of the human c-Ha-ras-1 gene. Cell 50: 711–717, 1987
Chang, T. D., Biedler, J. L., Stockert, E., and Old, L. J.: Trisomy of chromosome 15 in x-ray induced mouse leukemia. (Abstract.) Proc Am Assoc Cancer Res 18: 225, 1977
Doolittle, R. F., Hunkapiller, M. W., Hood, L. E., Devare, S. G., Robbins, K. C., Aaronson, S. A., and Antoniades, H. N.: Simian sarcoma virus onc gene, v-sis, is derived from the gene (or genes) encoding a platelet-derived growth factor. Science 221: 275–277, 1983
Ehrlich, M. and Wang, R. Y. H.: S-methylcytosine in eukaryotic DNA. Science 212: 1350–1357, 1981
Gelman, E. P., Wong-Staal, F., Kramer, R. A., and Gallo, R. C.: Molecular cloning and comparative analysis of the genomes of simian sarcoma virus and its associated helper virus. Proc Natl Acad Sci USA 78: 3373–3377, 1981
Haas, M., Mally, M. I., Bogenberger, M., Bogart, M. H., Buchanan, M. A., Augery-Bourget, Y., Hyman, R., and Vogt, M.: Autocrine growth and progression of murine x-ray-induced T cell lymphomas. EMBO J 5: 1775–1782, 1986
Heldin, C. H. and Westermark, B.: Growth factors: mechanism of action and relation to oncogenes. Cell 37: 9–20, 1984
Jackson, P. A. and Cook, P. R.: A general method for preparing chromatin containing intact DNA. EMBO J 4: 913–918, 1985
Jones, P. A.: DNA methylation and cancer. Cancer Res 46: 461–466, 1986
Kohtz, D. S. and Waksal, S. D.: Growth factors and leukemogenesis. Surv Immunol Res 3: 34–38, 1984
Le Clair, K. P., Rabin, M., Nesbitt, M. N., Pravtcheva, D., Ruddle, F. H., Palfree, R. G. E., and Bothwell, A.: Murine Ly-6 multigene family is located on chromosome 15. Proc Natl Acad Sci USA 84: 1638–1642, 1987
Malek, T. R., Ortega, G., Chan, C., Kroczek, R. A., and Shevach, E.: Role of Ly-6 in lymphocyte activation. J Exp Med 164: 709–722, 1986
Meruelo, D. and Rossomando, A.: A molecular and genetic approach to understanding the mechanisms by which fractionated x-irradiation induces leukemia in mice. Leuk Res 10: 819–832, 1986
Meruelo, D., Offer, M., and Flieger, N.: Genetics of susceptibility to radiation induced leukemia. Mapping of genes involved to chromosome 1, 2, and 4. Implications for a viral etiology in the disease. J Exp Med 154: 1201–1211, 1981a
Meruelo, D., Paolino, A., Flieger, N., Offer, M., and Dworkin, J.: Ly-11.2: a cell surface antigen that may identify murine lymphocytes susceptible to transformation by oncogenic agents. Fed Proc 40: 2717–2720, 1981b
Meruelo, D., Offer, M., and Rossomando, A.: Induction of leukemia by both fractionated-x-irradiation and radiation leukemia virus involves loci in the chromosome 2 segment coding for H-30-Agouti. Proc Natl Acad Sci USA 80: 462–466, 1983
Meruelo, D., Kornreich, R., Rossomando, A., Pampeno, C., Boral, A., Silver, J. L., Buxbaum, J., Weiss, E. H., Devlin, J. J., Mellor, A. L., Flavell, R. A., and Pellicer, A.: Lack of class I H-2 antigens in cells transformed by radiation leukemia virus is associated with methylation and rearrangement of H-2 DNA. Proc Natl Acad Sci USA 83: 4504–4508, 1986
Meruelo, D., Rossomando, A., Scandalis, S., D'Eustachio, P., Fournier, R. E. K., Roop, D. R., Saxe, D., Blatt, C., and Nesbitt, M. N.: Assignment of the Ly-6--Ril-1--Sis--H-30--Pol-5/Xmmv-72--Ins-3--Krt-1--Int-1--Gdc-1 region to mouse chromosome 15. Immunogenetics 25: 361–372, 1987
Nelson, M. and McClelland, M.: The effect of site-specific methylation on restriction-modification enzymes. Nucleic Acids Res 15: 219–230, 1987
Ortega, G., Korty, P. E., Shevach, E. M., and Malek, T. R.: Role of Ly-6 in lymphocyte activation. I. Characterization of monoclonal antibody to a nonpolymorphic Ly-6 specificity. J Immunol 137: 3240–3246, 1986
Ramsden, M., Cole, G., Smith, J., and Balmain, A.: Differential methylation of the c-H-ras gene in normal mouse cells and during skin tumor progression. EMBO J 4: 1449–1454, 1985
Robbins, K. C., Devare, S. G., Reddy, E. P., and Aaronson, S. A.: In vivo identification of the transforming gene product of simian sarcoma virus. Science 218: 1131–1133, 1982
Roberts, R. J.: Restriction enzymes and their isoschizomers. Nucleic Acids Res 15: 189–217, 1987
Rossomando, A. and Meruelo, D.: Viral sequences are associated with many histocompatibility genes. Immunogenetics 23: 233–245, 1986
Southern, E. M.: Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol 98: 503–517, 1975
Spira, J., Babonits, M., Weiner, F., Ohno, S., Wirschubski, Z., Haran-Ghera, N., and Klein, G.: Nonrandom chromosomal changes in the Thy-1 positive and the Thy-1 negative lymphomas induced by 7,12 demethylbenzanthracene in SJL mice. Cancer Res 40: 2609–2616, 1980
Swan, D. C., McBride, O. W., Robbins, K. C., Keithley, D. A., Reddy, E. P., and Aaronson, S. A.: Chromosomal mapping of the simian sarcoma virus onc gene analogue in human cells. Proc Natl Acad Sci USA 79: 4691–4695, 1982
Waterfield, M. D., Scrace, G. T., Whittle, N., Stroubant, P., Johnsson, A., Wasteson, A., Westermark, B., Heldin, C. H., Huang, J. S., and Deuel, T. F.: Platelet-derived growth factor is structurally related to the putative transforming protein p28sis of simian sarcoma virus. Nature 304: 35–39, 1983
Weiner, F., Ohno, S., Spira, J., Haran-Ghera, N., and Klein, J.: Chromosome changes (trisomies #15 and 17) associated with tumor progression in leukemias induced by radiation leukemia virus. J Natl Cancer Inst 61: 227–233, 1978
Weiner, F., Babonits, M., Haran-Ghera, N., and Klein, G.: Non-random duplication of chromosome 15 in murine T cell leukemias: further studies on translocation heterozygotes. Int J Cancer 26: 661–668, 1980
Woolf, T., Eric, L., Kronenberg, M., and Hood, L.: Mapping genomic organization by field inversion and two-dimensional gel electrophoresis: application to the murine T-cell receptor gene family. Nucleic Acids Res 16: 3863–3875, 1988
Youssoufian, H. and Mulder, C.: Detection of methylated sequences in eukaryotic DNA with the restriction endonucleases SmaI and XmaI. J Mol Biol 150: 133–136, 1981
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Address correspondence and offprint request to: N. M. B. Amari.
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Amari, N.M.B., Kamiura, S. & Meruelo, D. Effects of fractionated x-irradiation on the Ly-6--Ril-1--Pol-5 region. Immunogenetics 32, 252–262 (1990). https://doi.org/10.1007/BF00187096
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DOI: https://doi.org/10.1007/BF00187096