Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Short Report
  • Published:

The ATM gene is a target for epigenetic silencing in locally advanced breast cancer

Oncogene volume 23, pages 9432–9437 (2004)Cite this article

A Corrigendum to this article was published on 10 March 2005

Abstract

Several epidemiological studies on ataxia–telangiectasia families indicate that obligate ATM heterozygotes display an elevated risk for developing breast cancer. However, a molecular basis for a potential link between diminished ATM function and sporadic breast malignancy remains elusive. Here, we show that 78% (18 out of a panel of 23) of surgically removed breast tumors (stage II or greater) displayed aberrant methylation of the ATM proximal promoter region as judged by methylation-specific PCR. Aberrant methylation of the ATM promoter was independently confirmed in several tumors by bisulfite sequencing. Moreover, bisulfite sequencing indicated that this region of the genome is subject to dense methylation. Further, we found a highly significant correlation (P=0.0006) between reduced ATM mRNA abundance, as measured by real-time RT–PCR, and aberrant methylation of the ATM gene promoter. These findings indicate that epigenetic silencing of ATM expression occurs in locally advanced breast tumors, and establish a link at the molecular level between reduced ATM function and sporadic breast malignancy.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  • Ai L, Vo QN, Zuo C, Li L, Ling W, Suen JY, Hanna E, Brown KD and Fan CY . (2004). Cancer Epidemiol. Biomarkers Prev., 13, 150–156.

  • Angele S, Treilleux I, Taniere P, Martel-Planche G, Vuillaume M, Bailly C, Bremond A, Montesano R and Hall J . (2000). Clin. Cancer Res., 6, 3536–3544.

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

  • Bebb DG, Yu Z, Chen J, Telatar M, Gelmon K, Phillips N, Gatti RA and Glickman BW . (1999). Br. J. Cancer, 80, 1979–1981.

  • Bernstein JL, Bernstein L, Thompson WD, Lynch CF, Malone KE, Teitelbaum SL, Olsen JH, Anton-Culver H, Boice JD, Rosenstein BS, Borresen-Dale AL, Gatti RA, Concannon P and Haile RW . (2003). Br. J. Cancer, 89, 1513–1516.

  • Byrd PJ, Cooper PR, Stankovic T, Kullar HS, Watts GD, Robinson PJ and Taylor MR . (1996). Hum. Mol. Genet., 5, 1785–1791.

  • Chenevix-Trench G, Spurdle AB, Gatei M, Kelly H, Marsh A, Chen X, Donn K, Cummings M, Nyholt D, Jenkins MA, Scott C, Pupo GM, Dork T, Bendix R, Kirk J, Tucker K, McCredie MR, Hopper JL, Sambrook J, Mann GJ and Khanna KK . (2002). J. Natl. Cancer Inst., 94, 205–215.

  • Easton DF . (1994). Int. J. Radiat. Biol., 66, S177–S182.

  • Esteller M, Corn PG, Baylin SB and Herman JG . (2001). Cancer Res., 61, 3225–3229.

  • Fang ZM, Lee CS, Sarris M, Kearsley JH, Murrell D, Lavin MF, Keating K and Clarke RA . (2001). Pathology, 33, 30–36.

  • 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.

  • Gueven N, Keating K, Fukao T, Loeffler H, Kondo N, Rodemann HP and Lavin MF . (2003). Genes Chromosomes Cancer, 38, 157–167.

  • Gueven N, Keating KE, Chen P, Fukao T, Khanna KK, Watters D, Rodemann PH and Lavin MF . (2001). J. Biol. Chem., 276, 8884–8891.

  • Herman JG, Graff JR, Myohanen S, Nelkin BD and Baylin SB . (1996). Proc. Natl. Acad. Sci. USA, 93, 9821–9826.

  • Jones PA and Baylin SB . (2002). Nat. Rev. Genet., 3, 415–428.

  • Kairouz R, Clarke RA, Marr PJ, Watters D, Lavin MF, Kearsley JH and Lee CS . (1999). Mol. Pathol., 52, 252–256.

  • Kim WJ, Vo QN, Shrivastav M, Lataxes TA and Brown KD . (2002). Oncogene, 21, 3864–3871.

  • Rotman G and Shiloh Y . (1998). Hum. Mol. Genet., 7, 1555–1563.

  • Shafman TD, Levitz S, Nixon AJ, Gibans LA, Nichols KE, Bell DW, Ishioka C, Isselbacher KJ, Gelman R, Garber J, Harris JR and Haber DA . (2000). Genes Chromosomes Cancer, 27, 124–129.

  • Swift M, Reitnauer PJ, Morrell D and Chase CL . (1987). N. Engl. J. Med., 316, 1289–1294.

  • Vo QN, Geradts J, Gulley ML, Boudreau DA, Bravo JC and Schneider BG . (2002). J. Clin. Pathol., 55, 669–675.

Download references

Acknowledgements

We thank Mr Alberto Delgado, Ms Megan Bronson, Ms Mamie Yu and Ms San-San Ng for expert technical assistance. This work was supported by grants from the NIH (R21 CA102220), the A-T Children's Project and the Louisiana Breast Cancer Task Force/Cancer Association of Greater New Orleans to KDB. QNV was supported, in part, by a postdoctoral fellowship from the Stanley S Scott Cancer Center.

Author information

Author notes

  1. Wan-Ju Kim & Kevin D Brown

    Present address: Department of Biochemistry and Molecular Biology, The Shands Cancer Center, University of Florida College of Medicine, Gainesville, FL, 32610, USA

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, New Orleans, LA, USA

    Quynh N Vo, Wan-Ju Kim & Kevin D Brown

  2. Stanley S Scott Cancer Center, LSU Health Sciences Center, New Orleans, LA, USA

    Quynh N Vo, Wan-Ju Kim, Luke Cvitanovic & Kevin D Brown

  3. Department of Surgery, New Orleans, LA, USA

    Luke Cvitanovic

  4. Department of Pathology, New Orleans, LA, USA

    Donald A Boudreau

  5. UCSF Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CA, USA

    David G Ginzinger

Authors
  1. Quynh N Vo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wan-Ju Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Luke Cvitanovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Donald A Boudreau
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. David G Ginzinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kevin D Brown
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kevin D Brown.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vo, Q., Kim, WJ., Cvitanovic, L. et al. The ATM gene is a target for epigenetic silencing in locally advanced breast cancer. Oncogene 23, 9432–9437 (2004). https://doi.org/10.1038/sj.onc.1208092

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1208092

Keywords

This article is cited by

Search

Advanced search

Quick links