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