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.

  • Original Paper
  • Published:

Microsatellite instability at tetranucleotide repeats in skin and bladder cancer

Abstract

Recently, a novel form of MSI has been described that occurs only at tetranucleotide repeat markers. This has been termed elevated microsatellite instability at selected tetranucleotide repeats (EMAST). EMAST has been related to alterations of the p53 gene, and to the nature of the repeat sequence. We initially tested whether loss of heterozygosity (LOH) at the p53 and the patched (ptch) genes was related to EMAST in a series of 61 non-melanoma skin cancer (NMSC) tumors. We then analysed a series of 57 primary bladder cancers for the presence of EMAST, testing whether this was related to mutation or expression of the p53 gene. In both NMSC and bladder tumors we found a high prevalence of EMAST (75.4 and 43.9%). In NMSC the prevalence of EMAST was higher in tumors that had either p53 or ptch LOH, although the difference was not statistically significant. There was a significant association of extensive EMAST (three or more loci) with mutations in p53 among the bladder cancer tumors, but no indication of elevated EMAST in tumors with abnormal p53 staining without mutation. The association of EMAST with p53 mutation was confined to non-invasive disease. Hence, EMAST likely reflects a particular pattern of somatic events that are interactive with p53 mutation, particularly common in skin cancer and limited to non-invasive disease in bladder cancer.

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

Access options

Buy this article

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

Figure 1

Similar content being viewed by others

References

  • Ahmadian A, Ren ZP, Williams C, Ponten F, Odeberg J, Ponten J, Uhlen M, Lundeberg J . 1998 Oncogene 17: 1837–1843

  • Ahrendt SA, Decker PA, Doffek K, Wang B, Xu L, Demeure MJ, Jen J, Sidransky D . 2000 Cancer Res. 60: 2488–2491

  • Boland Cr, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, Meltzer SJ, Rodriguez-Bigas MA, Fodde R, Ranzani GN, Srivastava S . 1998 Cancer Res. 58: 5248–5257

  • Chuang YY, Chen Q, Brown JP, Sedivy JM, Liber HL . 1999 Cancer Res. 59: 3073–3076

  • Fearon ER, Vogelstein B . 1990 Cell 61: 759–767

  • Fujii K, Suzuki N, Ishijima S, Kita K, Sonoda T, Dezawa M, Sugita K, Niimi H . 1997 Biochem. Biophys. Res. Comm. 240: 269–272

  • Fujii K, Miyashita T, Takanashi J, Sugita K, Kohno Y, Nishie H, Yasumoto S, Furue M, Yamada M . 1999 Jap. J. Cancer Res. 90: 1351–1357

  • Gailani MR, Bale SJ, Leffell DJ, DiGiovanna JJ, Peck GL, Poliak S, Drum MA, Pastakia B, McBride OW, Kase R, Greene M, Mulvihill JJ, Bale AE . 1992 Cell 69: 111–117

  • Gibbs M, Collick A, Kelly RG, Jeffreys AJ . 1993 Genomics 17: 121–128

  • Hahn H, Wicking C, Zaphiropoulos PG, Gailani AR, Shanley S, Chidambaram A, Voreschovsky I, Holmberg E, Unden AB, Gillies S, Negus K, Smyth I, Pressman C, Leffell DJ, Gerrard B, Goldstein AM, Dean M, Toftgard R, Chenevix-Trench G, Wainwright B, Bale AE . 1996 Cell 85: 841–851

  • Hartwell LH, Kasten MB . 1994 Science 266: 1821–1828

  • Johnson RL, Rothman AL, Xie J, Goodrich LV, Bare JW, Bonifas JM, Quinn AG, Myers RM, Cox DR, Epstein Jr EH, Scott MP . 1996 Science 272: 1668–1671

  • Karagas MR, Greenberg ER, Spencer SK, Stukel TA, Mott LA . 1999 Int. J. Cancer 81: 555–559

  • Karagas MR, Tosteson TD, Blum J, Morris JS, Baron JA, Klaue B . 1998 Environ. Hlth. Perspect. 106: 1047–1050

  • Kuerbitzt SJ, Plunkett BS, Walsh WV, Kasten MB . 1992 Proc. Natl. Acad. Sci. USA 89: 7491–7495

  • Lichter MD, Karagas MR, Mott LA, Stukel TA, Greenberg ER . 2000 Arch. Dermatol. 136: 1007–1011

  • Little JB . 2000 Carinogenesis 21: 397–404

  • Livingstone L, White A, Sprouse J, Livanos E, Jacks T, Tlsty TD . 1992 Cell 70: 923–935

  • Loeb LA . 1991 Cancer Res. 51: 3075–3079

  • Loeb KR, Loeb LA . 2000 Carcinogenesis 21: 379–385

  • Lu X, Magrane G, Yin C, Louis DN, Gray J, Van Dyke T . 2001 Mol. Cell. Biol. 21: 6017–6030

  • Nagasawa H, Burke MJ, Little FF, McCone EF, Chan GL, Little JB . 1988 Terat. Carcin. Mut. 8: 25–33

  • Nelson HH, Wiencke JK, Gunn L, Wain JC, Christiani DC, Kelsey KT . 1998 Cancer Res. 58: 1804–1807

  • Ouhtit A, Nakazawa H, Armstrong BK, Kricker A, Tan E, Yamasaki H, English DR . 1998 J. Natl. Cancer Int. 90: 523–531

  • Ren ZP, Ahamadian A, Ponten F, Nister M, Berg C, Lundeberg J, Uhlen M, Pontzen J . 1997 Am. J. Pathol. 150: 1791–1803

  • Shen T, Park WS, Boni R, Saini N, Pham T, Lash AE, Vortmeyer AO, Zhuang Z . 1999 Hum. Pathol. 30: 284–287

  • Sidransky D . 1996 Nature 14: 7–8

  • Sidransky D, Hollestein M . 1996 Ann. Rev. Med. 47: 285–301

  • Toguchida J, Yamaguchi T, Ritchie B, Beauchamp RL, Dayton SH, Herrera GE, Yamamuro T, Kotoura Y, Sasaki MS, Little JB . 1992 Cancer Res. 52: 6194–6196

  • Vogelstein B, Kinzler KW . 1993 Trends Genet. 9: 138–141

  • Xu L, Chow J, Bonacum J, Eisenberger C, Ahrendt SA, Spafford M, Wu L, Lee SM, Piantadosi S, Tockman MS, Sidransky D, Jen J . 2001 Int. J. Cancer 91: 200–204

Download references

Acknowledgements

The authors would like to thank Dr Howard Liber, Dr Joseph Paulauskis and Dr John B Little for helpful discussion, and Megan Bronson, Virginia Stannard, Rachel Dow and Christine Hodorowski for technical assistance. Supported by: NIH grants P42ES5947, P42ES07373, CA09078, CA82354, CA57494 and ES00002.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Karl T Kelsey.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Danaee, H., Nelson, H., Karagas, M. et al. Microsatellite instability at tetranucleotide repeats in skin and bladder cancer. Oncogene 21, 4894–4899 (2002). https://doi.org/10.1038/sj.onc.1205619

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1205619

Keywords

This article is cited by

Search

Quick links