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  • Original Paper
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11q23.1 and 11q25-qter YACs suppress tumour growth in vivo

Abstract

Frequent allelic deletion at chromosome 11q22-q23.1 has been described in breast cancer and a number of other malignancies, suggesting putative tumour suppressor gene(s) within the 8 Mb deleted region. In addition, we recently described another locus, at the 11q25-qter region, frequently deleted in breast cancer, suggesting additional tumour suppressor gene(s) in this 2 Mb deleted region. An 11q YAC contig was accessed and three YACs, one containing the candidate gene ATM at 11q23.1, and two contiguous YACs (overlapping for 400 – 600 kb) overlying most of the 11q25 deleted region, were retrofitted with a G418 resistance marker and transfected into murine A9 fibrosarcoma cells. Selected A9 transfectant clones (and control untransfected and `irrelevant' alphoid YAC transfectant A9 clones) were assayed for in vivo tumorigenicity in athymic female Balb c-nu/nu mice. All the 11q YAC transfectant clones demonstrated significant tumour suppression compared to the control untransfected and `irrelevant' YAC transfected A9 cells. These results define two discrete tumour suppressor loci on chromosome 11q by functional complementation, one to a 1.2 Mb region on 11q23.1 (containing the ATM locus) and another to a 400 – 600 kb subterminal region on 11q25-qter.

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References

  • Athma P, Rappaport R and Swift M. . 1996 Cancer Genet. Cytogenet. 92: 130–134.

  • Baffa R, Negrini M, Mandes B, Rugge M, Ranzani GN, Hirohashi S and Croce CM. . 1996 Cancer Res. 56: 268–272.

  • Bethwaite PB, Koreth J, Herrington CS and McGee JO. . 1995 Br. J. Cancer 71: 814–818.

  • Carter SL, Negrini M, Baffa R, Gillum DR, Rosenberg AL, Schwartz GF and Croce CM. . 1994 Cancer Res. 54: 6270–6274.

  • Davis M, Hitchcock A, Foulkes WD and Campbell IG. . 1996 Cancer Res. 56: 741–744.

  • Dohner H, Stilgenbauer S, James MR, Benner A, Weilguni T, Bentz M, Fischer K, Hunstein W and Lichter P. . 1997 Blood 89: 2516–2522.

  • Easton DF. . 1994 Int. J. Radiat. Biol. 66: 6270–6274.

  • FitzGerald MG, Bean JM, Hegde SR, Unsal H, MacDonald DJ, Harkin DP, Finkelstein DM, Isselbacher KJ and Haber DA. . 1997 Nat. Genet. 15: 307–310.

  • Foulkes WD, Campbell IG, Stamp GW and Trowsdale J. . 1993 Br. J. Cancer 67: 268–273.

  • Gabra H, Taylor L, Cohen BB, Lessels A, Eccles DM, Leonard RC, Smyth JF and Steel CM. . 1995 Br. J. Cancer 72: 367–375.

  • Gabra H, Watson JE, Taylor KJ, Mackay J, Leonard RC, Steel CM, Porteous DJ and Smyth JF. . 1996 Cancer Res. 56: 950–954.

  • Gioeli D, Conway K and Weissman BE. . 1997 Cancer Res. 57: 1157–1165.

  • Hampton GM, Mannermaa A, Winquist R, Alavaikko M, Blanco G, Taskinen PJ, Kiviniemi H, Newsham I, Cavenee WK and Evans GA. . 1994 Cancer Res. 54: 4586–4589.

  • Hampton GM, Penny LA, Baergen RN, Larson A, Brewer C, Liao S, Busby ER, Williams AW, Steel CM, Bird CC and Stanbridge EJ. . 1994 Proc. Natl. Acad. Sci. USA 91: 6953–6957.

  • Herbst RA, Larson A, Weiss J, Cavenee WK, Hampton GM and Arden KC. . 1995 Cancer Res. 55: 2494–2496.

  • Hirst MC, Rack K, Nakahori Y, Roche A, Bell MV, Flynn G, Christadoulou Z, MacKinnon RN, Francis M, Littler AJ, Poustka A-M, Lehrach H, Schlessinger D, D'Urso M, Buckle VJ and Davies KE. . 1991 Nucleic Acids Res. 19: 3283–3288.

  • Horikawa I, Okamoto A, Yokota J and Oshimura M. . 1995 Cancer Genet. Cytogenet. 85: 97–100.

  • Huxley C, Hagino Y, Schlessinger D and Olson MV. . 1991 Genomics 9: 742–745.

  • Iizuka M, Sugiyama Y, Shiraishi M, Jones C and Sekiya T. . 19945 Genes Chromosomes Cancer 13: 40–46.

  • James MR, Richard CW, Schott JJ, Yousry C, Clark K, Bell J, Terwilliger JD, Hazan J, Dubay C, Vignal A, Agrapart M, Imai T, Nakamura Y, Polymeropoulos M, Weissenbach J, Cox DR and Lathrop GM. . 1994 Nat. Genet. 8: 70–76.

  • Keldysh PL, Dragani TA, Fleischman EW, Konstantinova LN, Perevoschikov AG, Pierotti MA, Della PG and Kopnin BP. . 1993 Genes Chromosomes Cancer 6: 45–50.

  • Killary AM, Wolf ME, Giambernardi TA and Naylor SA. . 1992 Proc. Natl. Acad. Sci. USA 89: 10877–10881.

  • Koreth J, Bakkenist CJ and McGee JO. . 1997 Oncogene 14: 431–437.

  • Koreth J, Bakkenist CJ and McGee JO. . 1998 J. Pathol. (in press).

  • Koreth J, Bethwaite PB and McGee JO. . 1995 J. Pathol. 176: 11–18.

  • Laake K, Odegard A, Andersen TI, Bukholm IK, Karesen R, Nesland JM, Ottestad L, Shiloh Y and Borresen-Dale A-L. . 1997 Genes Chromosom. Cancer 18: 175–180.

  • Larin Z. . 1995 Pulsed Field Gel Electrophoresis: A Practical Approach. AP Monaco (ed.).. IRL Press: Oxford pp.139–158.

    Google Scholar 

  • Markie D, Ragoussis J, Senger G, Rowan A, Sansom D, Trowsdale J, Sheer D and Bodmer WF. . 1993 Somatic Cell Molec. Genetics 19: 161–169.

  • Negrini M, Rasio D, Hampton GM, Sabbioni S, Rattan S, Carter SL, Rosenberg AL, Schwartz GF, Shiloh Y, Cavenee WK and Croce CM. . 1995 Cancer Res. 55: 3003–3007.

  • Negrini M, Sabbioni S, Possati L, Rattan S, Corallini A, Barbanti BG and Croce CM. . 1994 Cancer Res. 54: 1331–1336.

  • Phillips KK, Welch DR, Miele ME, Lee JH, Wei LL and Weissman BE. . 1996 Cancer Res. 56: 1222–1227.

  • Rasio D, Negrini M, Manenti G, Dragani TA and Croce CM. . 1995 Cancer Res. 55: 3988–3991.

  • Robertson G, Coleman A and Lugo TG. . 1996 Cancer Res. 56: 4487–4492.

  • Savitsky K, Ziv Y, Bar-Shira A, Gilad S, Tagle DA, Smith S, Uziel T, Sfez S, Nahmias J, Sartiel A, Eddy RL, Shows TB, Povey S, Collins FS, Shiloh Y and Rotman G. . 1996 Genomics 33: 199–206.

  • Sedgwick RP and Boder E. . 1991 Vinken PJ, Bruyn GW and Klawans HL, (eds). Handbook of clinical neurology. Elsevier: New York pp.347–423.

    Google Scholar 

  • Shaw ME and Knowles MA. . 1995 Genes Chromosomes Cancer 13: 1–8.

  • Shiloh Y. . 1994 Eur. J. Hum. Genet. 3: 116–138.

  • Srivatsan ES, Benedict WF and Stanbridge EJ. . 1986 Cancer Res. 46: 6174–6179.

  • Stilgenbauer S, Liebisch P, James MR, Schroder M, Schlegelberger B, Fischer K, Bentz M, Lichter P and Dohner H. . 1996 Proc. Natl. Acad. Sci. USA 93: 11837–11841.

  • Swift M, Morrell D, Massey RB and Chase CL. . 1991 N. Engl. J. Med. 325: 1831–1836.

  • Todd MC, Xiang R-H, Garcia DK, Kerbacher KE, Moore SL, Hensel CH, Liu P, Siciliano MJ, Kok K, van den Berg A, Veldhuis P, Buys CHCM, Killary AM and Naylor SL. . 1996 Oncogene 13: 2387–2396.

  • Tomlinson IP and Bodmer WF. . 1996 J. Clin. Pathol. 49: 386–390.

  • van Heyningen V and Little PF. . 1995 Cytogenet. Cell. Genet. 69: 127–158.

  • Vorechovsky I, Rasio D, Luo L, Monaco C, Hammarstrom L, Webster ADB, Zaloudik J, Barbanti-Brodano G, James M, Russo G, Croce CM and Negrini M . 1996 Cancer Res. 56: 2726–2732.

  • Winqvist R, Hampton GM, Mannermaa A, Blanco G, Alavaikko M, Kiviniemi H, Taskinen PJ, Evans GA, Wright FA, Newsham I and Cavenee WK. . 1995 Cancer Res. 55: 2660–2664.

  • Zakian VA. . 1995 Cell 82: 685–687.

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Koreth, J., Bakkenist, C., Larin, Z. et al. 11q23.1 and 11q25-qter YACs suppress tumour growth in vivo. Oncogene 18, 1157–1164 (1999). https://doi.org/10.1038/sj.onc.1202372

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