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Sequence rearrangements and genome instability

A possible step in carcinogenesis

  • Guest Editorial
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Summary

A substantial part of the mammalian genome is composed of sequences that do not contain structural genes. These sequences may constitute the major target for physical, chemical and biological DNA-damaging agents and can be involved in carcinogenesis. DNA-damaging agents contribute to the instability of the genome by introducing recombination-prone sites at DNA; these agents lead to extensive chromosal lesions and rearrangements of genes and their regulatory sequences. Movable sequences that exist and operate in certain bacteria, yeast, and the fruit fly are responsible for sequence rearrangements and contribute to the majority of mutations. Their presence and role in higher animals is not well established. Extensive chromosomal rearrangements were identified in numerous malignancies in man and animals and definitly seem to represent a characteristic of malignancy. Vast chromosomal damage and sequence reshuffling may be of no less importance in the malignant transformation than the point mutation of a particular gene.

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References

  • Albertini AM, Hofer M, Calos MP, Miller JH (1982) On the formation of spontaneous deletions: The importance of short sequence homologies in the generation of large deletions. Cell 29:319–328

    Article  Google Scholar 

  • Alitalo K, Schwab M, Lin CC, Varmus HE, Bishop JM (1983) Homogeneously staining chromosomal regions contain amplified copies of an abundantly expressed cellular oncogene (c-myc) in malignant neuroendocrine cells from a human colon carcinoma. Proc Natl Acad Sci USA 80:1707–1711

    PubMed  Google Scholar 

  • Arlett CF, Lehmann AR (1978) Human disorders showing increased sensitivity to the induction of genetic damage. Ann Rev Genet 12:95–115

    Article  PubMed  Google Scholar 

  • Bender W, Akam M, Karch F, Beachy PA, Peifer M, Spierer P, Lewis EB, Hogness DS (1983) Molecular genetics of the bithorax complex in Drosophila melanogaster. Science 221:23–29

    Google Scholar 

  • Battey, J, Moulding C, Taub R, Murphy W, Stewart T, Potter H, Lenoir G, Leder P (1983) The human c-myc oncogene: structural consequences of translocation into the IgH locus in Burkitt lymphoma. Cell 34:779–787

    PubMed  Google Scholar 

  • Cairns J (1981) The origin of human cancers Nature 289:353–357

    PubMed  Google Scholar 

  • Calabretta B, Robberson DL, Barrera-Saldana HA, Lambrou TP, Saunders GF (1982) Genome instability in a region of human DNA enriched in Alu repeat sequences. Nature 296:219–225

    PubMed  Google Scholar 

  • Calos MP, Miller JH (1980) Transposable elements. Cell 26:579–595

    Article  Google Scholar 

  • Calos MP, Lebkowski JS, Botchan MR (1983) High mutation frequency in DNA transfected into mammalian cells. Proc Natl Acad Sci USA 80:3015–3019

    PubMed  Google Scholar 

  • Canaani E, Dreazen O, Klar A, Rechavi G, Ram D, Cohen YB, Givol D (1983) Activation of the c-moc oncogene in a mouse plasmacytoma by insertion of an endogenous intracisternal A-particle genome. Proc Natl Acad Sci USA 80:7118–7122

    PubMed  Google Scholar 

  • Chao L, Vargas C, Spear BB, Cox EC (1983) Transposable elements as mutator genes in evolution. Nature 303:633–635

    PubMed  Google Scholar 

  • Chorąży M, Szala S (1983) Cellular transforming genes (Pol) Post Biochem 29:261–298

    Google Scholar 

  • Cooper GM (1982) Cellular transforming genes. Science 218:801–806

    Google Scholar 

  • Collins S, Groudine M (1982) Amplification of endogenous myc-related DNA sequences in a human myeloid leukaemia cell line. Nature 298:679–681

    PubMed  Google Scholar 

  • Collins SJ, Groudine MT (1983) Rearrangement and amplification of c-abl sequences in the human chronic myelogenous leukemia cell line K-562. Proc Natl Acad Sci USA 80:4813–4817

    PubMed  Google Scholar 

  • Cory S, Gerondakis S, Adams JM (1983) Interchromosomal recombination of the cellular oncogene c-myc with the immunoglobulin haevy chain locus in murine plasmacytomas is a reciprocal exchange. EMBO J 2:697–703

    PubMed  Google Scholar 

  • Croce CM, Thierfelder W, Erikson J, Nishikura K, Finan J, Lenoir GM, Nowell PC (1983) Transcriptional activation of an unrearranged and untranslocated c-myc oncogene by translocation of a C locus in Burkitt lymphoma cells. Proc Natl Acad Sci USA 80:6922–6926

    PubMed  Google Scholar 

  • Dalla Favera R, Wong-Staal F, Gallo RC (1982) onc gene amplification in promyelocytic leukaemia cell line HL-60 and primary leukaemic cells of the same patient. Nature 299:61–63

    PubMed  Google Scholar 

  • Deininger PL, Jolly DJ, Rubin CM, Friedmann T, Schmid CW (1981) Base sequence studies of 300 nucleotide renatured repeated human DNA clones. J Mol Biol 151:17–33

    PubMed  Google Scholar 

  • Dunnick W, Shell BE, Dery C (1983) DNA sequences near the site of reciprocal recombination between a c-myc oncogene and an immunoglobulin switch region. Proc Natl Acad Sci USA 80:7269–7273

    PubMed  Google Scholar 

  • Eisenstark A (1977) Genetic recombination in bacteria. Ann Rev Genet 11:369–396

    Article  PubMed  Google Scholar 

  • Emerit I, Gerutti PA (1981) Tumour promoter phorbol-12-myristate-13-acetate induces chromosomal damage via indirect action. Nature 293:144–146

    PubMed  Google Scholar 

  • Erikson J, Finan J, Nowell PC, Croce CM (1982) Translocation of immunoglobulin VH genes in Burkitt lymphoma. Proc Natl Acad Sci USA 79:5611–5615

    PubMed  Google Scholar 

  • Galloway DA, McDougall JK (1983) The oncogenic potential of herpes simplex viruses: evidence for a “hit-and-run” mechanism. Nature 301:21–24

    Google Scholar 

  • Gelmann EP, Psallidopoulos MC, Papas TS, Dalla-Favera R (1983) Identification of reciprocal translocation sites within the c-myc oncogene and immunoglobulin u locus in a Burkitt lymphoma. Nature 306:799–803

    PubMed  Google Scholar 

  • Hamlyn PH, Rabbits TH (1983) Translocation joins c-myc and immunoglobulin 1 genes in a Burkitt lymphoma revealing a third exon in the c-myc oncogene. Nature 304:135–139

    PubMed  Google Scholar 

  • Harris LJ, D'Eustachio P, Ruddle FH, Marcu KB (1982) DNA sequence associated with chromosome translocations in mouse plasmacytomas. Proc Natl Acad Sci USA 79:6622–6626

    PubMed  Google Scholar 

  • Hayday AC, Gillies SD, Saito H, Wood C, Wiman K, Hayward WS, Tonegawa S (1984) Activation of a translocated human c-myc gene by an enhancer in the immunoglobulin heavy-chain locus. Nature 307:334–340

    PubMed  Google Scholar 

  • Hayward WS, Neel BG, Astrin SM (1981) Activation of a cellular onc gene by promoter insertion in ALV-induced lymphoid leukosis. Nature 290:475–480

    PubMed  Google Scholar 

  • Hemminki K (1983) Nucleic acid adducts of chemical carcinogens and mutagens. Arch Toxicol 52:249–285

    Article  PubMed  Google Scholar 

  • Humphries P (1981) Consistent molecular genetic variation in human gastrointestinal carcinomas. Nature 293:146–148

    PubMed  Google Scholar 

  • Jariwalla RJ, Aurelian L, Ts'o POP (1983) Immortalization and neoplastic transformation of normal diploid cells by defined cloned DNA fragments of herpes simplex virus type 2. Proc Nat Acad Sci USA 80:5902–5906

    PubMed  Google Scholar 

  • Kleckner N (1977) Translocatable elements in procaryotes. Cell 11:11–23

    Article  PubMed  Google Scholar 

  • Klein G (1981) The role of gene dosage and genetic transpositions in carcinogenesis. Nature 294:313–318

    PubMed  Google Scholar 

  • Klein G (1983) Specific chromosomal translocations and the genesis of B-cell-derived tumors in mice and men. Cell 32:311–315

    Article  PubMed  Google Scholar 

  • Klein BY (1981) Can tumorigenesis result from in vivo “transfection” of a normal cell with DNA escaped from disintegrating nontransformed cells? J theor Biol 90:199–211

    PubMed  Google Scholar 

  • Kohl NE, Kanda N, Schreck RR, Bruns G, Latt SA, Gilbert F, Alt FW (1983) Transposition and amplification of oncogene-related sequences in human neuroblastomas. Cell 35:359–367

    Article  PubMed  Google Scholar 

  • Krolewski JJ, Bertelsen AH, Humayun MZ, Rush MG (1982) Members of the Alu family of interspersed, repetitive DNA sequences are in the small circular DNA population of monkey cells grown in culture. J Mol Biol 154:399–415

    PubMed  Google Scholar 

  • Lavi S (1981) Carcinogen-mediated amplification of viral DNA sequences in simian virus 40-transformed Chinese hamster embryo cells. Proc Natl Acad Sci USA 78:6144–6148

    PubMed  Google Scholar 

  • Lehmann AR (1982) Xeroderma pigmentosum, Cockayne syndrome and ataxia-telangiectasia: Disorders relating DNA repair to carcinogenesis. Cancer Surveys 1:93–118

    Google Scholar 

  • Little CD, Nau MM, Carney DN, Gazdar AF, Minna JD (1983) Amplification and expression of the c-myc oncogene in human lung cancer cell lines. Nature 306:194–196

    PubMed  Google Scholar 

  • Marcu KB, Harris LJ, Stanton LW, Erikson J, Watt R, Croce CM (1983) Transcriptionally active c-myc oncogene is contained within NIARD, a DNA sequence associated with chromosome translocations in B-cell neoplasia. Proc Nat Acad Sci USA 80:519–523

    PubMed  Google Scholar 

  • McClintock B (1956) Genetic mechanisms: structure and function. Cold Spring Harbor Symp Quant Biol 21:197–212

    PubMed  Google Scholar 

  • Miller CK, Temin HM (1983) High-efficiency ligation and recombination of DNA fragments by vertebrate cells. Science 220:606–609

    PubMed  Google Scholar 

  • Mushinski JF, Potter M, Bauer SR, Reddy EP (1983) DNA rearrangement and altered RNA expression of the c-myb oncogene in mouse plasmacytoid lymphosarcomas. Science 220:795–798

    PubMed  Google Scholar 

  • Nevers P, Saedler H (1977) Transposable genetic elements as agents of gene instability and chromosomal rearrangements. Nature 268:109–115

    PubMed  Google Scholar 

  • Payne GS, Bishop JM, Varmus HE (1982) Multiple arrangements of viral DNA and an activated host oncogene in bursal lymphomas. Nature 295:209–214

    PubMed  Google Scholar 

  • Rabbitts TH, Forster A, Baer R, Hamlyn PH (1983) Transcription enhancer identified near the human Cu immunoglobulin heavy chain gene is unavailable to the translocated c-myc gene in a Burkitt lymphomas. Nature 306:806–809

    PubMed  Google Scholar 

  • Rabbitts TH, Hamlyn PH, Baer R (1983) Altered nucleotide sequences of a translocated c-myc gene in Burkitt lymphoma. Nature 306:760–765

    PubMed  Google Scholar 

  • Radman M, Jeggo P, Wagner R (1982) Chromosomal rearrangement and carcinogenesis. Mut Res 98:249–264

    Google Scholar 

  • Rechavi G, Givol D, Canaani E (1982) Activation of a cellular oncogene by DNA rearrangement: possible involvement of an IS-like element. Nature 300:607–611

    PubMed  Google Scholar 

  • Reis RJS, Lumpkin Jr CK, McGill JR, Riabowol KT, Goldstein S (1983) Extrachromosomal circular copies of an “inter-Alu” unstable sequence in human DNA are amplified during in vitro and in vivo ageing. Nature 301:394–398

    PubMed  Google Scholar 

  • Rowley JD (1982) Identification of the constant chromosome regions involved in human hematologic malignant disease. Science 216:749–750

    PubMed  Google Scholar 

  • Sager R, Anisowicz A, Howell N (1981) Genomic rearrangements in a mouse cell line containing integrated SV40 DNA. Cell 23:41–50

    Article  PubMed  Google Scholar 

  • Schmid CW, Jelinek WR (1982) The Alu family of dispersed repetitive sequences. Science 216:1065–1070

    PubMed  Google Scholar 

  • Schwab M, Alitalo K, Varmus HE, Bishop JM, George D (1983) A cellular oncogene (c-Ki-ras) is amplified, overexpressed, and located within karyotypic abnormalities in mouse adrenocortical tumour cells. Nature 303:497–501

    PubMed  Google Scholar 

  • Selden JR, Emanuel BS, Wang E, Cannizzaro L, Palumbo A, Erikson J, Nowell PC, Rovera G, Croce CM (1983) Amplified C and c-abl genes are on the same marker chromosome in K562 leukemia cells. Proc Natl Acad Sci USA 80:7289–7292

    PubMed  Google Scholar 

  • Singer MF (1982) Highly repeated sequences in mammalian genomes. Int Rev Cyt 76:67–112

    PubMed  Google Scholar 

  • Singer B, Kuśmierek JT (1982) Chemical mutagenesis. Ann Rev Biochem 52:655–693

    Article  Google Scholar 

  • Smith GR, Schultz DW, Crasemann JM (1980) Generalized recombination: nucleotide sequence homology between Chi recombinational hotspots. Cell 19:785–793

    PubMed  Google Scholar 

  • Spradling AC, Rubin GM (1981) Drosophila genome organization: conserved and dynamic aspects. Ann Rev Genet 15:219–264

    Article  PubMed  Google Scholar 

  • Stanton LW, Watt R, Marcu KB (1983) Translocation breakage and truncated transcripts of c-myc oncogene in murine plasmacytomas. Nature 303:401–406

    PubMed  Google Scholar 

  • Trosko JE, Chang C-C (1978) Relationship between mutagenesis and carcinogenesis. Photochem Photobiol 28:157–168

    PubMed  Google Scholar 

  • Wintersberger U (1982) Chemical carcinogenesis — the price for DNA-repair? Naturwissenschaften 69:107–113

    PubMed  Google Scholar 

  • Yunis JJ (1983) The chromosomal basis of human neoplasia. Science 221:227–236

    PubMed  Google Scholar 

Download references

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Authors and Affiliations

  1. Department of Tumor Biology, Institute of Oncology, 44-100, Gliwice, Poland

    Mieczysław Chorąży

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  1. Mieczysław Chorąży
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The “Journal of Cancer Research and Clinical Oncology” publishes in loose succession “Editorials” and “Guest Editorials” on current and/or controversial problems in experimental and clinical oncology. These contributions represent exclusively the personal opinion of the author.

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Chorąży, M. Sequence rearrangements and genome instability. J Cancer Res Clin Oncol 109, 159–172 (1985). https://doi.org/10.1007/BF00390351

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  • DOI: https://doi.org/10.1007/BF00390351

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