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Searching for microsatellite mutations in coding regions in lung, breast, ovarian and colorectal cancers

Oncogene volume 20, pages 1005–1009 (2001)Cite this article

Abstract

RepX represents a new informatics approach to probe the UniGene database for potentially polymorphic repeat sequences in the open reading frame (ORF) of genes, 56% of which were found to be actually polymorphic. We now have performed mutational analysis of 17 such sites in genes not found to be polymorphic (<0.03 frequency) in a large panel of human cancer genomic DNAs derived from 31 lung, 21 breast, seven ovarian, 21 (13 microsatellite instability (MSI)+ and eight MSI−) colorectal cancer cell lines. In the lung, breast and ovarian tumor DNAs we found no mutations (<0.03–0.04 rate of tumor associated open reading frame mutations) in these sequences. By contrast, 18 MSI+ colorectal cancers (13 cancer cell lines and five primary tumors) with mismatch repair defects exhibited six mutations in three of the 17 genes (SREBP-2, TAN-1, GR6) (P<0.000003 compared to all other cancers tested). We conclude that coding region microsatellite alterations are rare in lung, breast, ovarian carcinomas and MSI (−) colorectal cancers, but are relatively frequent in MSI (+) colorectal cancers with mismatch repair deficits.

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Abbreviations

MSI:

microsatellite instability

SCLC:

small cell lung cancer

NSCLC:

non small cell lung cancer

SSCP:

single-stranded conformational polymorphism

RT–PCR:

reverse transcriptase polymerase chain reaction

MMR:

mismatch repair

References

  • Andrew SE, Goldberg YP, Kremer B, Telenius H, Theilmann J, Adam S, Starr E, Squitieri F, Lin B, Kalchman MA, Graham RK and Hayden MR. . 1993 Nat. Genet. 4: 398–403.

  • Bidichandani SI, Ashizawa T and Patel PI. . 1998 Am. J. Hum. Genet. 62: 111–121.

  • 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 Liskay RN. . 1994 Nature 368: 258–261.

  • Ellisen LW, Bird J, West DC, Soreng AL, Reynolds TC, Smith SD and Sklar J. . 1991 Cell 66: 649–661.

  • Fondon III JW, Mele GM, Brezinschek RI, Cummings D, Pande A, Wren J, O'Brien KM, Kupfer KC, Wei MH, Lerman M, Minna JD and Garner HR. . 1998 Proc. Natl. Acad. Sci. USA 95: 7514–7519.

  • Girard L, Hanna Z, Beaulieu N, Hoemann CD, Simard C, Kozak CA and Jolicoeur P. . 1996 Genes Dev. 10: 1930–1944.

  • Gurin CC, Federici MG, Kang L and Boyd J. . 1999 Cancer Res. 59: 462–466.

  • Herman JG, Umar A, Polyak K, Graff JR, Ahuja N, Issa JP, Markowitz S, Willson JK, Hamilton SR, Kinzler KW, Kane MF, Kolodner RD, Vogelstein B, Kunkel TA and Baylin SB. . 1998 Proc. Natl. Acad. Sci. USA 95: 6870–6875.

  • Hua X, Yokoyama C, Wu J, Briggs MR, Brown MS, Goldstein JL and Wang X. . 1993 Proc. Natl. Acad. Sci. USA 90: 11603–11607.

  • Jakupciak JP and Wells RD. . 1999 J. Biol. Chem. 274: 23468–23479.

  • King BL, Peng HQ, Goss P, Huan S, Bronson D, Kacinski BM and Hogg D. . 1997 Cancer Res. 57: 209–214.

  • Liu B, Nicolaides NC, Markowitz S, Willson JK, Parsons RE, Jen J, Papadopolous N, Peltomaki P, de la Chapelle A, Hamilton SR, Kinzler KW and Vogelstein B. . 1995 Nat. 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 T, Tannergard P, Hackman P, Rubio C, Kressner U, Lindmark G, Hellgren D, Lambert B and Lindblom A. . 1999 Human Genet. 105: 437–441.

  • 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.

  • Matuoka K, Miki H, Takahashi K and Takenawa T. . 1997 Biochem. Biophys. Res. Commun. 239: 488–492.

  • 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, Peterson GM, de la Chapelle A, Vogelstein B and Kinzler KW. . 1994 Nature 371: 75–80.

  • Orth K, Hung J, Gazdar A, Bowcock A, Mathis JM and Sambrook J. . 1994 Proc. Natl. Acad. Sci. USA 91: 9495–9499.

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

  • Pekarsky Y, Rynditch A, Wieser R, Fonatsch C and Gardiner K. . 1997 Cancer Res. 57: 3914–3919.

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

  • Satijn DP, Olson DJ, van der Vlag J, Hamer KM, Lambrechts C, Masselink H, Gunster MJ, Sewalt RG, van Driel R and Otte AP. . 1997 Mol. Cell Biol. 17: 6076–6086.

  • Wells RD. . 1996 J. Biol. Chem. 271: 2875–2878.

  • Wren JD, Forgacs E, Fondon III, JW, Pertsemlidis A, Cheng SY, Gallardo T, Williams RS, Shohet RV, Minna JD and Garner HR. . 2000 Am. J. Hum. Genet. 67: 345–356.

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

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Acknowledgements

The authors thank James Lutterbaugh and Dr Donald Lombardi for tumor cell lines, and Luc Girard for helpful comments on this manuscript. This work has been supported by the National Cancer Institute Lung Cancer SPORE grant P50 CA70907, G Harold and Leila Y Mathers Charitable Foundation. HR Garner is supported by the Patrick O'Brien Montgomery Distinguished Chair. S Markowitz is an associate investigator of the Howard Hughes Medical Institute, and was also supported by PHS-CA 67409.

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Authors and Affiliations

  1. The Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-8593, Texas, USA

    Eva Forgacs, Craig Kamibayashi, Masashi Kondo, Xie L Xu, Gail E Tomlinson, Carolyn Y Muller, Adi F Gazdar & John D Minna

  2. Program of Genetics and Development, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-8593, Texas, USA

    Jonathan D Wren

  3. Department of Pathology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-8593, Texas, USA

    Adi F Gazdar

  4. Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-8593, Texas, USA

    Harold R Garner & John D Minna

  5. Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-8593, Texas, USA

    Harold R Garner

  6. McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-8593, Texas, USA

    Harold R Garner

  7. Center for Biomedical Inventions, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-8593, Texas, USA

    Harold R Garner

  8. Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-8593, Texas, USA

    John D Minna

  9. Howard Hughes Medical Institute, Case Western Reserve University, Cleveland, OH 44106, Ohio, USA

    Sanford Markowitz

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  1. Eva Forgacs
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Forgacs, E., Wren, J., Kamibayashi, C. et al. Searching for microsatellite mutations in coding regions in lung, breast, ovarian and colorectal cancers. Oncogene 20, 1005–1009 (2001). https://doi.org/10.1038/sj.onc.1204211

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