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Hypermethylation of 14-3-3 σ (stratifin) is an early event in breast cancer

Oncogene volume 20, pages 3348–3353 (2001)Cite this article

Abstract

We have identified 14-3-3 σ (σ) as a gene whose expression is lost in breast carcinomas, primarily by methylation-mediated silencing. In this report, we investigated the timing of loss of σ gene expression during breast tumorigenesis in vivo. We analysed the methylation status of σ in breast cancer precursor lesions using microdissection for selective tissue sampling. We found hypermethylation of σ in 24 of 25 carcinomas (96%), 15 of 18 (83%) of ductal carcinoma in situ, and three of eight (38%) of atypical hyperplasias. None of the five hyperplasias without atypia showed σ-hypermethylation. Unexpectedly, patients with breast cancer showed σ hypermethylation in adjacent histologically normal breast epithelium, while this was never observed in individuals without evidence of breast cancer. Also, samples of periductal stromal breast tissue were consistently hypermethylated, underscoring the importance of selective tissue sampling for accurate assessment of 14-3-3-σ methylation in breast epithelium. These results suggest that hypermethylation of 14-3-3-σ occurs at an early stage in the progression to invasive breast cancer, and may occur in apparently normal epithelium adjacent to breast cancer. These results provide evidence that loss of expression of σ is an early event in neoplastic transformation.

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References

  • Baylin SB, Herman JG, Graff JR, Vertino PM, Issa JP . 1998 Adv. Cancer Res. 72: 141–196

  • Botti C, Pescatore B, Mottolese M, Sciarretta F, Greco C, Di Filippo F, Gandolfo GM, Cavaliere F, Bovani R, Varanese A, Cianciulli AM . 2000 J. Am. Coll. Surg. 190: 530–539

  • Chan TA, Hermeking H, Lengauer C, Kinzler KW, Vogelstein B . 1999 Nature 401: 616–620

  • Dellambra E, Golisano O, Bondanza S, Siviero E, Lacal P, Molinari M, D'Atri S, De Luca M . 2000 J. Cell. Biol. 149: 1117–1130

  • Deng G, Lu Y, Zlotnikov G, Thor AD, Smith HS . 1996 Science 274: 2057–2059

  • Emmert-Buck MR, Bonner RF, Smith PD, Chuaqui RF, Zhuang Z, Goldstein SR, Weiss RA, Liotta LA . 1996 Science 274: 998–1001

  • Ferguson AT, Evron E, Umbricht CB, Pandita TK, Chan TA, Hermeking H, Marks JR, Lambers AR, Futreal PA, Stampfer MR, Sukumar S . 2000 Proc. Natl. Acad. Sci. USA 97: 6049–6054

  • Fu H, Subramanian RR, Masters SC . 2000 Annu. Rev. Pharmacol Toxicol 40: 617–647

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

  • Nacht M, Ferguson AT, Zhang W, Petroziello JM, Cook BP, Gao YH, Maguire S, Riley D, Coppola G, Landes GM, Madden SL, Sukumar S . 1999 Cancer Res. 59: 5464–5470

  • Prasad GL, Valverius EM, McDuffie E, Cooper HL . 1992 Cell. Growth Differ. 3: 507–513

  • Robertson KD, Jones PA . 2000 Carcinogenesis 21: 461–467

  • Sidransky D . 1997 Science 278: 1054–1059

  • Soria JC, Gauthier LR, Raymond E, Granotier C, Morat L, Armand JP, Boussin FD, Sabatier L . 1999 Clin. Cancer Res. 5: 971–975

  • Umbricht CB, Sherman ME, Dome J, Carey LA, Marks J, Kim N, Sukumar S . 1999 Oncogene 18: 3407–3414

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Acknowledgements

This research was funded by grants from Susan G Komen Foundation {(BCTR 200 577 (SS), and Postdoctoral Fellowship Grant #9610 (CBU)}, P21 CA/ES 66204, and NIH Spore in Breast Cancer (P50 CA88843-01) to S Sukumar.

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Authors and Affiliations

  1. Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, 21231, Maryland, MD, USA

    Christopher B Umbricht

  2. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, 21231, Maryland, MD, USA

    Ella Evron & Saraswati Sukumar

  3. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, 21231, Maryland, MD, USA

    Edward Gabrielson

  4. Molecular Devices Corp., Sunnyvale, 94085, California, CA, USA

    Anne Ferguson

  5. Duke University Medical Center, Durham, 27710, North Carolina, NC, USA

    Jeffrey Marks

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  1. Christopher B Umbricht
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Umbricht, C., Evron, E., Gabrielson, E. et al. Hypermethylation of 14-3-3 σ (stratifin) is an early event in breast cancer. Oncogene 20, 3348–3353 (2001). https://doi.org/10.1038/sj.onc.1204438

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