Biopolym. Cell. 1998; 14(5):389-395.
Огляди
Мутаційний процес, пов'язаний з розвитком канцерогенезу: роль ALU повторів у генетичній нестабільності.
1Швачко Л. П.
  1. Інститут молекулярної біології і генетики НАН України
    Вул. Академіка Заболотного, 150, Київ, Україна, 03680

Abstract

В огляді розглядається можлива участь ALU повторів, мобільних генетичних елементів, у молекулярних механізмах нестабільності геному при канцерогенезі. Обговорюється роль повторів ДНК в утворенні делецій як важливої особливості структурних перебудов при канцерогенезі. Часто точки розривів ДНК при утворенні делецій знаходяться поблизу локусів, збагачених ALU послідовностями. ALU повтори переважно зустрічаються в R-смугах хромосом – місцях активної транскрипції, мітотичного кросинговеру і хромосомних транслокацій. Припускається, що ALU елементи як регуляторні елементи геному с не лише місцями переважної локалізації хромосомних транслокацій і утворення злитих (fusion) генів при канцерогенезі, але й несуть функціональну відповідальність за їхнє утворення, у зв'язку з чим можуть бути генетичними маркерами в ранньому розпізнаванні структурних перебудов геному.

References

[1] Bishop JM. Molecular origins of cancer. Ed. R. A. Weinberg. New York: Cold Spring Harbor Lab. press, 1989. 367 p.
[2] Bishop JM. Molecular themes in oncogenesis. Cell. 1991;64(2):235-48.
[3] Honchel R, Halling KC, Thibodeau SN. Genomic instability in neoplasia. Semin Cell Biol. 1995;6(1):45–52.
[4] Mao L, Lee DJ, Tockman MS, Erozan YS, Askin F, Sidransky D. Microsatellite alterations as clonal markers for the detection of human cancer. Proc Natl Acad Sci U S A. 1994;91(21):9871-5.
[5] Wahls WP, Wallace LJ, Moore PD. Hypervariable minisatellite DNA is a hotspot for homologous recombination in human cells. Cell. 1990;60(1):95-103.
[6] Ionov Y, Peinado MA, Malkhosyan S, Shibata D, Perucho M. Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. Nature. 1993;363(6429):558-61.
[7] Lukash LL, Shvachko LP, Kostetskaya KV. Mobile genetic elements in mutagenic process, recombination and malignization of human cells. Biopolym Cell. 1996;12(2):7-19.
[8] Barrett JC, Ts'o PO. Relationship between somatic mutation and neoplastic transformation. Proc Natl Acad Sci U S A. 1978;75(7):3297-301.
[9] Moolgavkar SH, Knudson AG Jr. Mutation and cancer: a model for human carcinogenesis. J Natl Cancer Inst. 1981;66(6):1037-52.
[10] Knudson AG Jr. Hereditary cancers of man. Cancer Invest. 1983;1(2):187-93.
[11] Rossi AM, Thijssen JC, Tates AD, Vrieling H, Natarajan AT, Lohman PH, van Zeeland AA. Mutations affecting RNA splicing in man are detected more frequently in somatic than in germ cells. Mutat Res. 1990;244(4):353-7.
[12] Strunnikov VA, Uryvaeva IV, Brodski? VIa. [Double-mutation hypothesis of carcinogenesis]. Tsitol Genet. 1984;18(5):380-91.
[13] Renan MJ. How many mutations are required for tumorigenesis? Implications from human cancer data. Mol Carcinog. 1993;7(3):139-46.
[14] Box HC, Budzinski EE, Freund HG, Evans MS, Patrzyc HB, Wallace JC, MacCubbin AE. Vicinal lesions in X-irradiated DNA? Int J Radiat Biol. 1993;64(3):261-3.
[15] Moskaleva Yu, Ilyushina IA. DNA damage by the action of ionizing radiation and their repair. Itogi nauki i tekhniki. M.: VINITI, (Ser. Radiatsionnaya biologiya; vol. 9) 1990: 3-113.
[16] Koufos A, Hansen MF, Copeland NG, Jenkins NA, Lampkin BC, Cavenee WK. Loss of heterozygosity in three embryonal tumours suggests a common pathogenetic mechanism. Nature. 1985 Jul 25-31;316(6026):330-4.
[17] Scrable HJ, Sapienza C, Cavenee WK. Genetic and epigenetic losses of heterozygosity in cancer predisposition and progression. Adv Cancer Res. 1990;54:25-62.
[18] Kolodner RD. Mismatch repair: mechanisms and relationship to cancer susceptibility. Trends Biochem Sci. 1995;20(10):397-401.
[19] Boyer JC, Umar A, Risinger JI, Lipford JR, Kane M, Yin S, Barrett JC, Kolodner RD, Kunkel TA. Microsatellite instability, mismatch repair deficiency, and genetic defects in human cancer cell lines. Cancer Res. 1995;55(24):6063-70.
[20] Kiselev FL. [Genes of DNA stabilization and carcinogenesis]. Mol Biol (Mosk). 1998;32(2):197-205.
[21] Perucho M, Peinado MA, Ionov Y, Casares S, Malkhosyan S, Stanbridge E. Defects in replication fidelity of simple repeated sequences reveal a new mutator mechanism for oncogenesis. Cold Spring Harb Symp Quant Biol. 1994;59:339-48.
[22] Perucho M. Cancer of the microsatellite mutator phenotype. Biol Chem. 1996;377(11):675-84.
[23] Fishel R, Lescoe MK, Rao MR, Copeland NG, Jenkins NA, Garber J, Kane M, Kolodner R. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell. 1993;75(5):1027-38.
[24] de Wind N, Dekker M, Berns A, Radman M, te Riele H. Inactivation of the mouse Msh2 gene results in mismatch repair deficiency, methylation tolerance, hyperrecombination, and predisposition to cancer. Cell. 1995;82(2):321-30.
[25] Mitchell GA, Labuda D, Fontaine G, Saudubray JM, Bonnefont JP, Lyonnet S, Brody LC, Steel G, Obie C, Valle D. Splice-mediated insertion of an Alu sequence inactivates ornithine delta-aminotransferase: a role for Alu elements in human mutation. Proc Natl Acad Sci U S A. 1991;88(3):815-9.
[26] Nguyen T, Marchese A, Kennedy JL, Petronis A, Peroutka SJ, Wu PH, O'Dowd BF. An Alu sequence interrupts a human 5-hydroxytryptamine1D receptor pseudogene. Gene. 1993;124(2):295-301.
[27] Ma TS, Ifegwu J, Watts L, Siciliano MJ, Roberts R, Perryman MB. Serial Alu sequence transposition interrupting a human B creatine kinase pseudogene. Genomics. 1991;10(2):390-9.
[28] Muratani K, Hada T, Yamamoto Y, Kaneko T, Shigeto Y, Ohue T, Furuyama J, Higashino K. Inactivation of the cholinesterase gene by Alu insertion: possible mechanism for human gene transposition. Proc Natl Acad Sci U S A. 1991;88(24):11315-9.
[29] Krajinovic M, Richer C, Labuda D, Sinnett D. Detection of a mutator phenotype in cancer cells by inter-Alu polymerase chain reaction. Cancer Res. 1996;56(12):2733-7.
[30] Jarnik M, Tang JQ, Korab-Laskowska M, Zietkiewicz E, Cardinal G, Gorska-Flipot I, Sinnett D, Labuda D. Overall informativity, OI, in DNA polymorphisms revealed by inter-Alu PCR: detection of genomic rearrangements. Genomics. 1996;36(3):388-98.
[31] L?zaro C, Gaona A, Ravella A, Volpini V, Casals T, Fuentes JJ, Estivill X. Novel alleles, hemizygosity and deletions at an Alu-repeat within the neurofibromatosis type 1 (NF1) gene. Hum Mol Genet. 1993;2(6):725-30.
[32] Harwood J, Tachibana A, Davis R, Bhattacharyya NP, Meuth M. High rate of multilocus deletion in a human tumor cell line. Hum Mol Genet. 1993;2(2):165-71.
[33] Kaden DA, Bardwell L, Newmark P, Anisowicz A, Skopek TR, Sager R. High frequency of large spontaneous deletions of DNA in tumor-derived CHEF cells. Proc Natl Acad Sci U S A. 1989;86(7):2306-10.
[34] Ponder B. Cancer. Gene losses in human tumours. Nature. 1988;335(6189):400-2.
[35] Krawczak M, Cooper DN. Gene deletions causing human genetic disease: mechanisms of mutagenesis and the role of the local DNA sequence environment. Hum Genet. 1991;86(5):425-41.
[36] Thacker J, Chalk J, Ganesh A, North P. A mechanism for deletion formation in DNA by human cell extracts: the involvement of short sequence repeats. Nucleic Acids Res. 1992;20(23):6183-8.
[37] Canning S, Dryja TP. Short, direct repeats at the breakpoints of deletions of the retinoblastoma gene. Proc Natl Acad Sci U S A. 1989;86(13):5044-8.
[38] Love DR, England SB, Speer A, Marsden RF, Bloomfield JF, Roche AL, Cross GS, Mountford RC, Smith TJ, Davies KE. Sequences of junction fragments in the deletion-prone region of the dystrophin gene. Genomics. 1991;10(1):57-67.
[39] Yen PH, Li XM, Tsai SP, Johnson C, Mohandas T, Shapiro LJ. Frequent deletions of the human X chromosome distal short arm result from recombination between low copy repetitive elements. Cell. 1990;61(4):603-10.
[40] R?diger NS, Hansen PS, J?rgensen M, Faergeman O, Bolund L, Gregersen N. Repetitive sequences involved in the recombination leading to deletion of exon 5 of the low-density-lipoprotein receptor gene in a patient with familial hypercholesterolemia. Eur J Biochem. 1991;198(1):107-11.
[41] Roth DB, Wilson JH. Nonhomologous recombination in mammalian cells: role for short sequence homologies in the joining reaction. Mol Cell Biol. 1986;6(12):4295-304.
[42] Mager DL, Goodchild NL. Homologous recombination between the LTRs of a human retrovirus-like element causes a 5-kb deletion in two siblings. Am J Hum Genet. 1989;45(6):848-54.
[43] Pfeiffer P, Thode S, Hancke J, Vielmetter W. Mechanisms of overlap formation in nonhomologous DNA end joining. Mol Cell Biol. 1994;14(2):888-95.
[44] Taghian DG, Hough H, Nickoloff JA. Biased short tract repair of palindromic loop mismatches in mammalian cells. Genetics. 1998;148(3):1257-68.
[45] Morris T, Thacker J. Formation of large deletions by illegitimate recombination in the HPRT gene of primary human fibroblasts. Proc Natl Acad Sci U S A. 1993;90(4):1392-6.
[46] Kunkel TA. Misalignment-mediated DNA synthesis errors. Biochemistry. 1990;29(35):8003-11.
[47] Phillips JW, Morgan WF. Illegitimate recombination induced by DNA double-strand breaks in a mammalian chromosome. Mol Cell Biol. 1994;14(9):5794-803.
[48] Lanza A, Tornaletti S, Rodolfo C, Scanavini MC, Pedrini AM. Human DNA topoisomerase I-mediated cleavages stimulated by ultraviolet light-induced DNA damage. J Biol Chem. 1996;271(12):6978-86.
[49] Bae YS, Kawasaki I, Ikeda H, Liu LF. Illegitimate recombination mediated by calf thymus DNA topoisomerase II in vitro. Proc Natl Acad Sci U S A. 1988;85(7):2076-80.
[50] Berkvens TM, van Ormondt H, Gerritsen EJ, Khan PM, van der Eb AJ. Identical 3250-bp deletion between two AluI repeats in the ADA genes of unrelated ADA-SCID patients. Genomics. 1990;7(4):486-90.
[51] Mauillon JL, Michel P, Limacher JM, Latouche JB, Dechelotte P, Charbonnier F, Martin C, Moreau V, Metayer J, Paillot B, Frebourg T. Identification of novel germline hMLH1 mutations including a 22 kb Alu-mediated deletion in patients with familial colorectal cancer. Cancer Res. 1996;56(24):5728-33.
[52] Myerowitz R, Hogikyan ND. A deletion involving Alu sequences in the beta-hexosaminidase alpha-chain gene of French Canadians with Tay-Sachs disease. J Biol Chem. 1987;262(32):15396-9.
[53] Stoppa-Lyonnet D, Carter PE, Meo T, Tosi M. Clusters of intragenic Alu repeats predispose the human C1 inhibitor locus to deleterious rearrangements. Proc Natl Acad Sci U S A. 1990;87(4):1551-5.
[54] Vnencak-Jones CL, Phillips JA 3rd. Hot spots for growth hormone gene deletions in homologous regions outside of Alu repeats. Science. 1990;250(4988):1745-8.
[55] Daniels GR, Deininger PL. Integration site preferences of the Alu family and similar repetitive DNA sequences. Nucleic Acids Res. 1985;13(24):8939-54.
[56] Rouyer F, Simmler MC, Page DC, Weissenbach J. A sex chromosome rearrangement in a human XX male caused by Alu-Alu recombination. Cell. 1987;51(3):417-25.
[57] Lehrman MA, Goldstein JL, Russell DW, Brown MS. Duplication of seven exons in LDL receptor gene caused by Alu-Alu recombination in a subject with familial hypercholesterolemia. Cell. 1987;48(5):827-35.
[58] Marcus S, Hellgren D, Lambert B, F?llstr?m SP, Wahlstr?m J. Duplication in the hypoxanthine phosphoribosyl-transferase gene caused by Alu-Alu recombination in a patient with Lesch Nyhan syndrome. Hum Genet. 1993;90(5):477-82.
[59] Ariga T, Carter PE, Davis AE 3rd. Recombinations between Alu repeat sequences that result in partial deletions within the C1 inhibitor gene. Genomics. 1990;8(4):607-13.
[60] Huang LS, Ripps ME, Korman SH, Deckelbaum RJ, Breslow JL. Hypobetalipoproteinemia due to an apolipoprotein B gene exon 21 deletion derived by Alu-Alu recombination. J Biol Chem. 1989;264(19):11394-400.
[61] Strout MP, Marcucci G, Bloomfield CD, Caligiuri MA. The partial tandem duplication of ALL1 (MLL) is consistently generated by Alu-mediated homologous recombination in acute myeloid leukemia. Proc Natl Acad Sci U S A. 1998;95(5):2390-5.
[62] Rothberg PG, Ponnuru S, Baker D, Bradley JF, Freeman AI, Cibis GW, Harris DJ, Heruth DP. A deletion polymorphism due to Alu-Alu recombination in intron 2 of the retinoblastoma gene: association with human gliomas. Mol Carcinog. 1997;19(2):69-73.
[63] Chen SJ, Chen Z, Font MP, d'Auriol L, Larsen CJ, Berger R. Structural alterations of the BCR and ABL genes in Ph1 positive acute leukemias with rearrangements in the BCR gene first intron: further evidence implicating Alu sequences in the chromosome translocation. Nucleic Acids Res. 1989;17(19):7631-42.
[64] Zabarovsky ER, Kashuba VI, Pokrovskaya ES, Zabarovska VI, Wang JY, Berglund P, Boldog F, Stanbridge EJ, Sumegi J, Klein G, et al. Alu-PCR approach to isolating NotI-linking clones from the 3p14-p21 region frequently deleted in renal cell carcinoma. Genomics. 1993;16(3):713-9.
[65] Bernard OA, Romana SP, Schichman SA, Mauchauff? M, Jonveaux P, Berger R. Partial duplication of HRX in acute leukemia with trisomy 11. Leukemia. 1995;9(9):1487-90.
[66] Macina RA, Barr FG, Galili N, Riethman HC. Genomic organization of the human PAX3 gene: DNA sequence analysis of the region disrupted in alveolar rhabdomyosarcoma. Genomics. 1995;26(1):1-8.
[67] Koduru PR, Goh JC, Pergolizzi RG, Lichtman SM, Broome JD. Molecular characterization of a variant Ph1 translocation t(9;22;11) (q34;q11;q13) in chronic myelogenous leukemia (CML) reveals the translocation of the 3'-part of BCR gene to the chromosome band 11q13. Oncogene. 1993;8(12):3239-47.
[68] Megonigal MD, Rappaport EF, Jones DH, Kim CS, Nowell PC, Lange BJ, Felix CA. Panhandle PCR strategy to amplify MLL genomic breakpoints in treatment-related leukemias. Proc Natl Acad Sci U S A. 1997;94(21):11583-8.
[69] Gu Y, Alder H, Nakamura T, Schichman SA, Prasad R, Canaani O, Saito H, Croce CM, Canaani E. Sequence analysis of the breakpoint cluster region in the ALL-1 gene involved in acute leukemia. Cancer Res. 1994;54(9):2327-30.
[70] von Lindern M, Breems D, van Baal S, Adriaansen H, Grosveld G. Characterization of the translocation breakpoint sequences of two DEK-CAN fusion genes present in t(6;9) acute myeloid leukemia and a SET-CAN fusion gene found in a case of acute undifferentiated leukemia. Genes Chromosomes Cancer. 1992;5(3):227-34.
[71] Schmid CW, Jelinek WR. The Alu family of dispersed repetitive sequences. Science. 1982;216(4550):1065-70.
[72] Slagel V, Flemington E, Traina-Dorge V, Bradshaw H, Deininger P. Clustering and subfamily relationships of the Alu family in the human genome. Mol Biol Evol. 1987;4(1):19-29.
[73] Maraia RJ, Driscoll CT, Bilyeu T, Hsu K, Darlington GJ. Multiple dispersed loci produce small cytoplasmic Alu RNA. Mol Cell Biol. 1993;13(7):4233-41.
[74] Calabretta B, Robberson DL, Barrera-Salda?a HA, Lambrou TP, Saunders GF. Genome instability in a region of human DNA enriched in Alu repeat sequences. Nature. 1982;296(5854):219-25.
[75] Filatov LV, Mamayeva SE, Tomilin NV. Alu family variations in neoplasia. Cancer Genet Cytogenet. 1991;56(1):11-22.
[76] Georgiev GP. Mobile genetic elements and carcinogenesis. Zh Vsesoyuz Khim Obsch im DI Mendeleeva. 1986; 31(3):100-6.
[77] Tomilin NV, Bozhkov VM. Human nuclear protein interacting with a conservative sequence motif of Alu-family DNA repeats. FEBS Lett. 1989;251(1-2):79-83.
[78] Tomilin NV, Iguchi-Ariga SM, Ariga H. Transcription and replication silencer element is present within conserved region of human Alu repeats interacting with nuclear protein. FEBS Lett. 1990;263(1):69-72.
[79] Tomilin NV. Modulation of gene expression by Alu retrotransposons and control their reproduction in the human genome. Proc. rep. 4th Intern. Conf. "AIDS, Cancer and Related Problems." Saint Petersburg. 1996: 168.
[80] Sidorov AV, Blinov VM, Borzykh OA, Sleptsova IA, Zverev VV. [Characteristics of the LTR of endogenous retrovirus in the human T-lymphocyte CD4 receptor gene]. Vopr Virusol. 1998;43(1):33-6.