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Mutated gene-specific phenotypes of dinucleotide repeat instability in human colorectal carcinoma cell lines deficient in DNA mismatch repair

Oncogene volume 18, pages 2143–2147 (1999)Cite this article

Abstract

Mutations in DNA mismatch repair (MMR) genes in hereditary non-polyposis colon cancer (HNPCC) patients revealed the importance of MMR deficiency as a risk for carcinogenesis. Since diverse mutations occur in several MMR genes, the instability of repeat sequences dispersed in the genome, which are also governed by the MMR system, is a well used marker. However, the relationship between repeat sequence instability and MMR gene mutation in human cells has not been well defined mainly because precise systems to analyse repeat sequences have not been available. Using our newly developed system, we analysed alteration of dinucleotide repeats in human cell lines which harbour mutations in MMR genes. Among 24 subclones of DLD-1 cells (hMSH6−) only one had a dinucleotide repeat alteration in only one microsatellite locus, while LoVo cells (hMSH2−/hMSH6−) exhibited marked dinucleotide repeat instability (DRI). HCT116 cells, a hMLH1-mutant, showed an ultimate DRI phenotype. Interestingly, SW48 cells lacking hMLH1 expression also demonstrated DRI, albeit the extent of diversity being significantly lower than HCT116. These data suggest that the DRI phenotype in human cells is highly dependent on mutated MMR genes and on forms of mutation. The results of DRI analyses used to detect MMR-deficiency should be interpreted with caution.

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References

  • Ahuja N, Mohan AL, Li Q, Stolker JM, Herman JG, Hamilton SR, Baylin SR and Issa JR. . 1997 Cancer Res. 57: 3370–3374.

  • Akiyama Y, Sato H, Yamada T, Nagasaki H, Tsuchiya A, Abe R and Yuasa Y. . 1997 Cancer Res. 57: 3920–3923.

  • Beck NE, Tomlinson IP, Homfray T, Frayling I, Hodgson SV, Harocopos C and Bodmer WF. . 1997 Hum. Genet. 99: 219–224.

  • Bhattacharyya NP, Skandalis A, Ganesh A, Groden J and Meuth M. . 1994 Proc. Natl. Acad. Sci. USA 91: 6319–6323.

  • Boyer JC, Umar A, Risinger JI, Lipford JR, Kane M, Yin S, Barrett JC, Kolodner RD and Kunkel TA. . 1995 Cancer Res. 55: 6063–6070.

  • Branch P, Hampson R and Karran P. . 1995 Cancer Res. 55: 2304–2309.

  • 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 Lisky RM. . 1994 Nature 368: 258–261.

  • Drummond JT, Li GM, Longley MJ and Modrich P. . 1995 Science 268: 1909–1912.

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

  • Herfarth KK, Kodner IJ, Whelan AJ, Ivanovich JL, Bracamontes JR, Wells SAJ and Goodfellow PJ. . 1997 Gen. Chrom. Cancer 18: 42–49.

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

  • Kowalski LD, Mutch DG, Herzog TJ, Rader JS and Goodfellow PJ. . 1997 Gen. Chrom. Cancer 18: 219–227.

  • Laemmli UK. . 1970 Nature 227: 680–685.

  • Leach FS, Nicolaides NC, Papadopoulos N, Liu B, Jen J, Parsons R, Peltomaki P, Sistonen P, Aaltonen LA, Nystrom-Lahti M, Guan XY, Zhang J, Meltzer PS, Yu JW, Kao FT, J. CD, Cerosaletti KM, Fournier REK, Todd S, Lewis T, Leach RJ, Naylor SL, Weissenbach J, Mecklin JP, Jarvinen 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.

  • Liu B, Nicolaides NC, Markowitz S, Willson JK, Parsons RE, Jen J, Papadopoulos N, Peltomaki P, de la Chapelle A, Hamilton SR, Kinzler KW and Vogelstein B. . 1995 Nature Genet. 9: 48–55.

  • Liu B, Parsons R, Papadopoulos N, Nicolaides NC, Lynch HT, Watson P, Jass JR, Dunlop M, Wyllie A, Peltomaki P, de la Chapelle A, Hamilton SR, Vogelstein B and Kinzler KW. . 1996 Nature Med. 2: 169–174.

  • Liu B, Parsons RE, Hamilton SR, Petersen GM, Lynch HT, Watson P, Markowitz S, Willson JK, Green J, de la Chapelle A, Kinzler KW and Vogelstein B. . 1994 Cancer Res. 54: 4590–4594.

  • Nakabeppu Y, Oda S and Sekiguchi M. . 1993 Mol. Cell. Biol. 13: 4157–4166.

  • Nicolaides NC, Papadopoulos N, Liu B, Wei YF, Carter KC, Ruben SM, Rosen CA, Haseltine WA, Fleischmann RD, Fraser CM, Adams MD, Venter JC, Dunlop MG, Hamilton SR, Petersen GM, de la Chapelle A, Vogelstein B and Kinzler KW. . 1994 Nature 371: 75–80.

  • Nystrom-Lahti M, Wu Y, Moisio AL, Hofstra RM, Osinga J, Mecklin JP, Jarvinen HJ, Leisti J, Buys CH, de la Chapelle A and Peltomaki P. . 1996 Hum. Mol. Genet. 5: 763–769.

  • Oda S, Oki E, Maehara Y and Sugimachi K. . 1997 Nucleic Acids Res. 25: 3415–3420.

  • Palombo F, Gallinari P, Iaccarino I, Lettieri T, Hughes M, D'Arrigo A, Truong O, Hsuan JJ and Jiricny J. . 1995 Science 268: 1912–1914.

  • Papadopoulos N, Nicolaides NC, Liu B, Parsons R, Lengauer C, Palombo F, D'Arrigo A, Markowitz S, Willson JK, Kinzler KW, Jiricny J and Vogelstein B. . 1995 Science 268: 1915–1917.

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

  • Parsons R, Li GM, Longley MJ, Fang WH, Papadopoulos N, Jen J, de la Chapelle A, Kinzler KW, Vogelstein B and Modrich P. . 1993 Cell 75: 1227–1236.

  • Schug MD, Mackay TF and Aquadro CF. . 1997 Nature Genet. 15: 99–102.

  • Shibata D, Peinado MA, Ionov Y, Malkhosyan S and Perucho M. . 1994 Nature Genet. 6: 273–281.

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

  • Thibodeau SN, French AJ, Roche PC, Cunningham JM, Tester DJ, Lindor NM, Moslein G, Baker SM, Liskay RM, Burgart LJ, Honchel R and Halling KC. . 1996 Cancer Res. 56: 4836–4840.

  • Weber TK, Conlon W, Petrelli NJ, Rodriguez-Bigas M, Keitz B, Pazik J, Farrell C, O'Malley L, Oshalim M, Abdo M, Anderson G, Stoler D and Yandell D. . 1997 Cancer Res. 57: 3798–3803.

  • Wu MS, Sheu JC, Shun CT, Lee WJ, Wang JT, Wang TH, Cheng AL and Lin JT. . 1997a Cancer Lett. 112: 161–166.

  • Wu Y, Nystrom-Lahti M, Osinga J, Looman MW, Peltomaki P, Aaltonen LA, de la Chapelle A, Hofstra RM and Buys CH. . 1997b Gen. Chrom. Cancer 18: 269–278.

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Acknowledgements

We are most grateful to M Sekiguchi for helpful advice and to M Ohara for comments on the manuscript. This study was supported by grants from the Ministry of Education, Science, Sports and Culture of Japan.

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Authors and Affiliations

  1. Cancer Center, Kyushu University Hospital, Fukuoka, 812-8582, Japan

    Eiji Oki, Shinya Oda, Yoshihiko Maehara & Keizo Sugimachi

  2. Department of Surgery II, Faculty of Medicine, Kyushu University, Fukuoka, 812-8582, Japan

    Keizo Sugimachi

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  1. Eiji Oki
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Oki, E., Oda, S., Maehara, Y. et al. Mutated gene-specific phenotypes of dinucleotide repeat instability in human colorectal carcinoma cell lines deficient in DNA mismatch repair. Oncogene 18, 2143–2147 (1999). https://doi.org/10.1038/sj.onc.1202583

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