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Variable mutation frequencies in coding repeats of TCF-4 and other target genes in colon, gastric and endometrial carcinoma showing microsatellite instability

Oncogene volume 18, pages 6806–6809 (1999)Cite this article

Abstract

Frameshift mutations in genes containing mononucleotide repeats are often observed in cancers exhibiting a high frequency of microsatellite instability (MSI-H). Several tumor types, including colorectal, gastric, and endometrial carcinomas, display this phenotype in a significant proportion of cases. We recently showed in a large series of MSI-H colorectal tumors that approximately 40% of them exhibited frameshift mutations in an (A)9 tract within the coding region of the TCF-4 gene, a crucial member of the APC/β-catenin/TCF pathway. In the present study, we have examined MSI-H cancers from other primary tumor sites for mutations in this new target gene. Two of 22 (9%) MSI-H primary gastric cancers and none of 23 MSI-H endometrial primary tumors and cell lines were found to have a 1 bp deletion in the TCF-4 repeat. In the same series of tumors we also looked for frameshift mutations in other coding repeats localized within the TGFβ-RII, BAX, IGFIIR, hMSH3 and hMSH6 genes. Our results suggest that the TCF-4 gene, in a similar manner to some of these latter genes, is differentially altered in MSI-H tumors from different primary sites.

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References

  • Aaltonen LA, Peltomäki P, Leach FS, Sistonen P, Pylkkänen L, Mecklin JP, Järvinen H, Powell SM, Jen J, Hamilton SR, Petersen GM, Kinzler KW, Vogelstein B and de la Chapelle A. . 1993 Science 260: 812–816.

  • Bronner CE, Baker SM, Morrison PT, Warren G, Smith LG, Lescoe MK, Kane M, Earabino C, Lipford J, Lindblom A, Tannergard P, Bollag RJ, Godwin AR, Ward DC, Nordenskjold M, Fishel R, Kolodner R and Laskay RM. . 1994 Nature 368: 258–261.

  • Candidus S, Bischoff P, Becker KF and Hofler H. . 1996 Cancer Res. 56: 49–52.

  • Duval A, Gayet J, Zhou XP, Iacopetta B, Thomas G and Hamelin R. . 1999 Cancer Res. 59: 4213–4215.

  • Fishel R, Lescoe MK, Rao MRS, Copeland NG, Jenkins NA, Garber J, Kane M and Kolodner R. . 1993 Cell 75: 1027–1038.

  • Fukuchi T, Sakamoto M, Tsuda H, Maruyama K, Nozawa S and Hirohashi S. . 1998 Cancer Res. 58: 3526–3528.

  • He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, Morin PJ, Vogelstein B and Kinzler KW. . 1998 Science 281: 1509–1512.

  • Hoang JM, Cottu PH, Thuille B, Salmon RJ, Thomas G and Hamelin R. . 1997 Cancer Res. 57: 300–303.

  • Horii A, Nakatsuru S, Miyoshi Y, Ichii S, Nagase H, Kato Y, Yanagisawa A and Nakamura Y. . 1992 Cancer Res. 52: 5231–5233.

  • Ionov Y, Peinado M, Malkhosyan S, Shibata D and Perucho M. . 1993 Nature 363: 558–561.

  • Korinek V, Barker N, Morin PJ, van Wichen D, de Weger R, Kinzler KW, Vogelstein B and Clevers H. . 1997 Science 275: 1784–1787.

  • Leach FS, Nicolaïdes NC, Papadopoulos N, Liu B, Jen J, Parsons R, Peltomaki P, Sistonen P, Aaltonen LA, Nyström-Lahti M, Guan X-Y, Zhang J, Meltzer PS, Yu JW, Kao FT, Chen DJ, Cerosaletti KM, Keith-Fournier RE, Todd S, Lewis T, Leach RJ, Naylor SL, Weissenbach J, Mecklin JP, Järvinen H, Petersen GM, Hamilton SR, Green J, Jass J, Watson P, Lynch HT, Trent JM, De la Chapelle A, Kinzler KW and Vogelstein B. . 1993 Cell 75: 1215–1225.

  • Malkhosyan S, Rampino N, Yamamoto H and Perucho M. . 1996 Nature 382: 499–500.

  • Markowitz S, Wang J, Myeroff L, Parsons R, Sun L, Lutterbaugh J, Fan RS, Zborowska E, Kinzler KW, Vogelstein B, Brattain M and Willson JKV. . 1995 Science 268: 1336–1338.

  • Morin PJ, Sparks AB, Korinek V, Barker N, Clevers H, Vogelstein B and Kinzler KW. . 1997 Science 275: 1787–1790.

  • Myeroff LL, Parsons R, Kim SJ, Hedrick L, Cho KR, Orth K, Mathis M, Kinzler KW, Lutterbaugh J, Park K, Bang YJ, Lee HY, Park JG, Lynch HT, Roberts AB, Vogelstein B and Markowitz SD. . 1995 Cancer Res. 55: 5545–5547.

  • Ogasawara S, Maesawa C, Tamura G and Satodate R. . 1994 Virchows Arch. 424: 607–611.

  • Papadopoulos N, Nicolaïdes NC, Wei YF, Ruben SM, Carter KC, Rosen CA, Haseltine WA, Fleishmann RD, Fraser CM, Adams MD, Venter JC, Hamilton SR, Petersen GM, Watson P, Lynch HT, Peltomäki P, Mecklin JP, De la Chapelle A, Kinzler KW and Vogelstein B. . 1994 Science 263: 1625–1629.

  • Parsons R, Myeroff LL, Liu B, Willson JKV, Markowitz SD, Kinzler KW and Vogelstein B. . 1995 Cancer Res. 55: 5548–5550.

  • Rampino N, Yamamoto H, Ionov Y, Li Y, Sawai H, Reed JC and Perucho M. . 1997 Science 275: 967–969.

  • Souza RF, Appel R, Yin J, Wang S, Smolinski KN, Abraham JM, Zou TT, Shi YQ, Lei J, Cottrell J, Cymes K, Biden K, Simms L, Leggett B, Lynch PM, Frazier M, Powell SM, Harpaz N, Sugimura H, Young J and Meltzer SJ. . 1996 Nature Genet. 14: 255–257.

  • Tamura G, Maesawa C, Suzuki Y, Tamada H, Satoh M, Ogasawara S, Kashiwaba M and Satodate R. . 1994 Cancer Res. 54: 1149–1151.

  • Thibodeau SN, Bren G and Schaid D. . 1993 Science 260: 816–819.

  • Wu MS, Lee CW, Shun CT, Wang HP, Lee WJ, Sheu JC and Lin JT. . 1998 Cancer Res. 58: 1494–1497.

  • Yamamoto H, Sawai H and Perucho M. . 1997 Cancer Res. 57: 4420–4426.

  • Zhou XP, Hoang JM, Li YJ, Seruca R, Carneiro F, Sobrinho-Simoes M, Lothe R, Gleeson CM, Hilary Russell SE, Muzeau F, Flejou JF, Hoang-Xuan K, Lidereau R, Thomas G and Hamelin R. . 1998 Genes Chromosom. Cancer 21: 101–107.

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Acknowledgements

A Duval was recipient of fellowship from the Lique Nationale contre le Cancer. This work was partly supported by grant 9624 from Association pour la Recherche sur le Cancer. We thank `l'équipe de séquençage du CEPH' for their help in sequencing.

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Authors and Affiliations

  1. INSERM U434-CEPH, 27, rue Juliette Dodu, Paris, 75010, France

    A Duval, G Thomas & R Hamelin

  2. Department of Surgery, University of Western Australia, Nedlands, Australia

    B Iacopetta

  3. Department of Genetics and Microbiology, University of Pavia, Italy

    G N Ranzani

  4. Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo, Norway

    R A Lothe

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  1. A Duval
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Duval, A., Iacopetta, B., Ranzani, G. et al. Variable mutation frequencies in coding repeats of TCF-4 and other target genes in colon, gastric and endometrial carcinoma showing microsatellite instability. Oncogene 18, 6806–6809 (1999). https://doi.org/10.1038/sj.onc.1203287

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