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  • Oncogenomics
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MBD1, MBD2 and CGBP genes at chromosome 18q21 are infrequently mutated in human colon and lung cancers

Oncogene volume 22, pages 3506–3510 (2003)Cite this article

Abstract

The genes MBD1 and MBD2 encode methyl-CpG binding proteins that suppress transcription from methylated promoters. In contrast, CGBP encodes a protein that binds promoters containing unmethylated CpG and stimulates transcription. All three are located on human chromosome 18q21, a region of frequent loss of heterozygosity in several cancers. These genes therefore represent candidate tumour suppressor genes, whose loss of function could affect the normal regulation of gene expression, whether by lack of complete suppression of genes normally silenced (via loss of MBD1 and MBD2) or by some loss of activation of genes normally expressed (via loss of CGBP), either way contributing to the tumorigenic phenotype. We have confirmed by fluorescent in situ hybridization that MBD1 and MBD2 bracket the DCC locus giving a gene order of MBD1/CGBP–DCC 5′-DCC 3′-MBD2. Mutation analyses by single-stranded conformation polymorphism in colon and lung cancer cell lines and primary tumours revealed a small number of mutations, suggesting only a limited role of these genes in human tumorigenesis.

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References

  • Bader S, Walker M, Hendrich B, Bird A, Bird C, Hooper M and Wyllie A . (1999). Oncogene, 18, 8044–8047.

  • Bhattacharya SK, Ramchandani S, Cervoni N and Szyf M . (1999). Nature, 397, 579–583.

  • Bestor TH and Verdine GL . (1994). Curr. Opin. Cell Biol., 6, 380–389.

  • Bird A . (2002). Genes Dev., 16, 6–21.

  • Boeke J, Ammerpohl O, Kegel S, Moehren U and Renkawitz R . (2000). J. Biol. Chem., 275, 34963–34967.

  • Carlone DL and Skalnik DG . (2001). Mol. Cell. Biol., 21, 7601–7606.

  • Cho KR, Oliner JD, Simons JW, Hedrick L, Fearon ER, Preisinger AC, Hedge P, Silverman GA and Vogelstein B . (1994). Genomics, 19, 525–531.

  • Cross SH, Clark CH and Bird AP . (1999). Nucleic Acids Res., 27, 2099–2107.

  • Cross SH, Meehan RR, Nan X and Bird A . (1997). Nat. Genet., 16, 256–259.

  • Detich N, Theberge J and Szyf M . (2002). J. Biol. Chem., 277, 35791–35794.

  • Fabre M, Martin M, Ulloa F and Real FX . (1999). Int J. Cancer, 81, 799–807.

  • Fazeli A, Dickinson SL, Hermiston ML, Tighe V, Steen RG, Small CC, Stoeckli ET, Keino-Masu K, Masu M, Rayburn H, Simons J, Bronson RT, Gordon JI, Tessier-Lavigne M and Weinberg RA . (1997). Nature, 386, 796–803.

  • Fearon ER, Cho KR, Nigro JM, Kern SE, Simmons JW, Ruppert JM, Hamilton SR, Preisinger AC, Thomus G, Kinzler KW and Vogelstein B . (1990). Science, 247, 49–56.

  • FitzGerald KT and Diaz MO . (1999). Genomics, 59, 187–192.

  • Fujita N, Shimotake N, Ohki I, Chiba T, Saya H, Shirakawa M and Nakao M . (2000). Mol. Cell. Biol., 20, 5107–5118.

  • Fujita N, Takebayashi S-I, Okumura K, Kudo S, Chiba T, Saya H and Nakao M . (1999). Mol. Cell. Biol., 19, 6415–6426.

  • Gu Y, Nakamura T, Alder H, Prasad R, Canaani O, Cimino G, Croce CM and Canaani E . (1992). Cell, 71, 701–708.

  • Guy J, Hendrich B, Holmes M, Martin JE and Bird A . (2001). Nat. Genet., 27, 322–326.

  • Hahn SA, Schutte M, Shamsul Hoque ATM, Moskaluk CA, da Costa LT, Rozenblum E, Weinstein CL, Fischer A, Yeo CJ, Hruban RH and Kern SE . (1996). Science, 271, 350–353.

  • Hendrich B, Abbott C, McQueen H, Chambers D, Cross S and Bird A . (1999a). Mammal. Genome, 10, 906–912.

  • Hendrich B, Guy J, Ramsahoye B, Wilson VA and Bird A . (2001). Genes Dev., 15, 710–723.

  • Hendrich B, Hardeland U, Ng H-H, Jiricny J and Bird A . (1999b). Nature, 401, 301–304.

  • Jen J, Kim H, Piantadosi S, Liu ZF, Levitt RC, Sistonen P, Kinzler KW, Vogelstein B and Hamilton SR . (1994). N Engl. J. Med., 28, 213–221.

  • Jones PL, Veenstra GJC, Wade PA, Vermaak D, Kass SU, Landsberger N, Strouboulis J and Wolffe AP . (1998). Nat. Genet., 19, 187–191.

  • Kanai Y, Ushijima S, Nakanishi Y and Hirohashi S . (1999). Biochem. Biophys. Res. Commun., 264, 962–966.

  • Lanza G, Matteuzzi M, Gafa R, Orvieto E, Maestri I, Santini A and del Senno L . (1998). Int. J. Cancer, 79, 390–395.

  • Ma Q, Alder H, Nelson KK, Chatterjee D, Gu Y, Nakamura T, Canaani E, Croce CM, Siracusa LD and Buchberg AM . (1993). Proc. Natl Acad. Sci. USA, 90, 6350–6354.

  • Martinez-Lopez E, Abad A, Font A, Monzo M, Ojanguren I, Pifarre A, Sanchez JJ, Martin C and Rosell R . (1998). Gastroenterology, 114, 1330–1338.

  • Müller-Tidow C, Kügler K, Diederichs S, Klümpen S, Möller M, Vogt U, Metzger R, Schneider PM, Berdel WE and Serve H . (2001). Br. J. Cancer, 85, 1168–1174.

  • Nan X, Meehan RR and Bird A . (1993). Nucleic Acids Res., 21, 4886–4892.

  • Nan X, Ng H-H, Johnson CA, Laherty CD, Turner BM, Eisenman RN and Bird A . (1998). Nature, 393, 386–389.

  • Ng H-H, Zhang Y, Hendrich B, Johnson CA, Turner BM, Erdjument-Bromage H, Tempst P, Reinberg D and Bird A . (1999). Nat. Genet., 23, 58–61.

  • Prasad R, Yano T, Sorio C, Nakamura T, Rallapalli R, Gu Y, Leshkowitz D, Croce CM and Canaani E . (1995). Proc. Natl Acad. Sci. USA, 92, 12160–12164.

  • Riggins GJ, Thiagalingam S, Rozenblum E, Weinstein CL, Kern SE, Hamilton SR, Willson KJKV, Markowitz SD, Kinzler KW and Vogelstein B . (1996). Nat. Genet., 13, 347–349.

  • Saito Y, Kanai Y, Sakamoto M, Saito H, Ishii H and Hirohashi S . (2001). Hepatology, 33, 561–568.

  • Sato M, Horio Y, Sekido Y, Minna JD, Shimokata K and Hasegawa Y . (2002). Oncogene, 21, 4822–4829.

  • Shiseki M, Kohno T, Nishikawa R, Sameshima Y, Mizoguchi H and Yokota J . (1994). Cancer Res., 54, 5643–5648.

  • Takai K, Kohno T, Hamada K, Takita J, Noguchi M, Matsuno Y, Hirohashi S, Uezato H and Yokota J . (1998). Cancer Res., 58, 3700–3705.

  • Thiagalingam S, Lengauer C, Leach FS, Schutte M, Hahn SA, Overhauser J, Willson JKV, Markowitz S, Hamilton SR, Kern SE, Kinzler KW and Vogelstein B . (1996). Nat. Genet., 13, 343–345.

  • Tkachuk DC, Kohler S and Cleary ML . (1992). Cell, 71, 691–700.

  • Virmani AK, Fong KM, Kodagoda D, McIntire D, Hung J, Tonk V, Minna JD and Gazdar AF . (1998). Genes, Chromosomes Cancer, 21, 308–319.

  • Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, Nakamura Y, White R, Smits AMM and Bos JL . (1988). N Engl. J. Med., 319, 525–532.

  • Vogelstein B, Fearon ER, Kern SE, Hamilton SR, Preisinger AC, Nakamura Y and White R . (1989). Science, 244, 207–211.

  • Voo KS, Carlone DL, Jacobsen BM, Flodin A and Skalnik DG . (2000). Mol. Cell. Biol., 20, 2108–2121.

  • Wade PA, GegonneA, Jones PL, Ballestar E, Aubry F and Wolffe AP . (1999). Nature Genet., 23, 62–66.

  • Zeleznik-Le NJ, Harden AM and Rowley J . (1994). Proc. Natl Acad. Sci. USA, 91, 10610–10614.

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Acknowledgements

We thank Drs John Minna and Adi Gazdar (UTSMC, Dallas) for DNAs of 60 of the lung cancer cell lines. Fixed preparations of human metaphase and interphase cells were a gift from Shelagh Boyle (MRC Human Genetics Unit, Edinburgh). This study was supported by the Cancer Research UK (SB, AP, DJH), Chief Scientist Office of the Scottish Executive (SB, MW), the BBSRC (HAMcQ) and the Wellcome Trust (APB).

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Authors and Affiliations

  1. Division of Pathology Molecular Medicine Centre, Sir Alastair Currie Cancer Research UK Laboratories, University of Edinburgh, Edinburgh, EH4 2XU, UK

    Scott Bader, Marion Walker, Robert Sellar, Elizabeth Oei, Suzan Wopereis, Yanhua Zhu, Audrey Peter & David J Harrison

  2. Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, EH9 3JR, UK

    Heather A McQueen & Adrian P Bird

  3. Instituut Life Science Technology, Enschede, 7500KB, The Netherlands

    Suzan Wopereis

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  1. Scott Bader
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Correspondence to Scott Bader.

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Bader, S., Walker, M., McQueen, H. et al. MBD1, MBD2 and CGBP genes at chromosome 18q21 are infrequently mutated in human colon and lung cancers. Oncogene 22, 3506–3510 (2003). https://doi.org/10.1038/sj.onc.1206574

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