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  • Original Paper
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Microsatellite instability in European hepatocellular carcinoma

Abstract

Genetic instability has been detected in many types of cancers but poorly investigated in hepatocellular carcinoma (HCC). We have studied the incidence of microsatellite instability (MI) at eight highly polymorphic microsatellite markers and the poly A tract BAT26 and tested for mutations at two sites of repetitive sequence (poly-A nucleotides 709 – 718 and GT repeat-nucleotides 1931 – 1936) in the Transforming Growth Factor β (TGFβ) type II receptor (RII) gene, in a group of 46 European HCCs and the surrounding nontumour tissue. This analysis showed that 63% of HCCs exhibit MI in at least one chromosome locus and 41% in two or more loci. No mutations of the TGFβRII gene were found in the MI positive tumours. No correlation was found with clinicopathological characteristics of the tumours such as cirrhosis, etiology, number of nodules, Edmondson's grade and vascular invasion. However, in patients who had a rearranged D16S402 microsatellite in their tumour, the recurrent disease and the number of nodules were significantly higher than in the others (P<0.005 and P<0.02, respectively). We propose to consider D16S402 rearrangement in HCC as a prognostic factor to identify patients presenting a higher risk of recurrence.

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References

  • Abe T, Ouyan H, Migita T, Kato Y, Kimura M, Shiiba K, Sunamura M, Matsuno S and Horii A. . 1996 Eur. J. Surg. Oncol. 22: 474–477.

  • Akashi Y, Koreeda C, Emomoto S, Uchiyama S, Mizumo T, Shiozaki Y, Sameshima Y and Imoue K. . 1991 Hepatology 14: 262–268.

    Article  CAS  Google Scholar 

  • Arzimanoglou IA, Lallas T, Osborne M, Barber H and Gilbert F. . 1996 Carcinogenesis 47: 1799–1804.

    Article  CAS  Google Scholar 

  • Bismuth H, Chiche L, Adam P, Castaing D, Diamond T and Dennison A. . 1993 Ann. Surg. 218: 145–151.

  • Boige V, Laurent-Puig P, Fouchet P, Fléjou JF, Monges G, Bedossa P, Bioulac-Sage P, Capron F, Schmitz A, Olschwang S and Thomas G. . 1997 Cancer Res. 57: 1986–1990.

  • Bourdon JC, D'Errico A, Paterlini P, Grigioni W, May E and Debuire B. . 1995 Gastroenterol. 108: 1176–1182.

  • Brentnall TA, Chen R, Lee JG, Kimmey MB, Bronner MP, Haggitt RC, Kowdley KV, Hecker LM and Byrd DR. . 1995 Cancer Res. 55: 4264–4267.

  • Brentnall TA, Crispin DA, Bronner P, Cherian SP, Hueffed M, Rabinovitch PS, Rubin CE, Haggitt RC and Boland R. . 1996 Cancer Res. 56: 1237–1240.

  • Chung YJ, Song JM, Lee JY, Jung YT, Seo JE, Choi SW and Rhyu MG. . 1996 Cancer Res. 56: 4662–4665.

  • De Marchis L, Contegiacomo A, D'Amico C, Palmirotta R, Pizzi C, Ottini L, Mastranzo P, Figliolini M, Petrella G, Amanti C, Battista P, Bianco AR, Frati L, Cama A and Costantini RM. . 1997 Clin. Cancer Res. 3: 241–248.

  • Duggan BD, Felix JC, Uderspach LI, Tourgeman D, Zheng J and Shibata D. . 1994 J. Natl. Cancer Inst. 86: 1216–1221.

  • Feray C, Gigou M, Samuel D, Paradis V, Wilber J, David MF, Urdea M, Reynes M, Brechot C and Bismuth H. . 1994 Hepatology 20: 1137–1143.

    PubMed  Google Scholar 

  • Gonzalez-Zulueta M, Ruppert JM, Tokino K, Tsai YC, Spruck III CH, Miyao N, Nichols PW, Hermann GG, Horn T, Steven K, Summerhayes IC, Sidransky D and Jones PA. . 1993 Cancer 53: 5620–5623.

  • Hann HJ, Yanagisawa A, Kato Y, Park JG and Nakamura Y. . 1993 Cancer Res. 53: 5087–5089.

  • Hoang JM, Cottu PH, Thuille B, Salmon RJ, Thomas G and Hamelin R. . 1996 Cancer Res. 53: 300–303.

  • Honchel R, Halling KC, Schaid DJ, Pittelkow M and Thibodeau SN. . 1994 Cancer Res. 54: 1159–1163.

  • Ionov Y, Peinado MA, Malkhosyan S, Shibata D and Perucho M. . 1993 Nature 363: 558–561.

    Article  CAS  Google Scholar 

  • Kaneko H, Horiike S, Taniwaki M and Misawa S. . 1996 Leukemia 10: 1696–1699.

  • Kaplanski C, Srivatanakul P and Wild CP. . 1997 Int. J. Cancer 72: 248–254.

    Article  CAS  Google Scholar 

  • Lemoine A, Le Bricon T, Salvucci M, Azoulay S, Pham P, Raccuia JS, Bismuth H and Debuire B. . 1997 Ann. Surg. 226: 43–50.

  • Lin HY, Wang XF, Ng-Eaton E, Weinberg RA and Lodish HF. . 1992 Cell 68: 775–785.

    Article  CAS  Google Scholar 

  • Lothe RA, Peltomaki P, Meling GI, Aaltonen L, Nystroöm-Lahti M, Pylkkänen L, Heimdal K, Andersen TI, Moller P, Rognum TO, Fossa SD, Haldorsen T, Langmark F, Brogger A, de la Chapelle A and Borresen AL. . 1993 Cancer Res. 53: 5849–5852.

  • Lu S, Akiyama Y, Nagasaki H, Saijo K and Yuasa Y. . 1995 Biochem. Biophys. Res. Commun. 216: 452–457.

  • Meltzer SJ, Yin J, Manin B, Rhuy MG, Cottrell J, Hudson E and Redd BJ. . 1994 Cancer Res. 54: 3379–3382.

  • Merlo A, Mabry M, Gabrielson E, Vollmer R, Baylin SB and Sidransky D. . 1994 Cancer Res. 54: 2098–2101.

  • Myeroff LL, Parsons R, Kim SJ, Hedrick L, Cho KR, Orth K, Mathis M, Kinzler KW, Lutterbaugh J, Park K, Bang YJ, Lee HY, Park JG, Lynch HT, Roberts AB, Vogelstein B and Markowitz SD. . 1995 Cancer Res. 55: 5545–5547.

  • Nagai H, Pineau P, Tiollais P, Buendia MA and Dejean A. . 1997 Oncogene 14: 2927–2933.

    Article  CAS  Google Scholar 

  • Parsons R, Myerhoff LL, Liu B, Wilson JKV, Markowitz SD, Kinzler KW and Vogelstein B. . 1995 Cancer Res. 55: 5548–5550.

  • Paulson TG, Wright FA, Parker BA, Russack V and Wahl G. . 1996 Cancer Res. 56: 4021–4026.

  • Polyak K. . 1996 Biochim. Biophys. Acta. 1424: 185–199.

  • Rhyu MG, Park WS and Meltzer SJ. . 1994 Oncogene 9: 29–32.

  • Salvucci M, Lemoine A, Azoulay D, Sebagh M, Bismuth H, Reynès M, May E and Debuire B. . 1996 Oncogene 13: 2681–2685.

  • Samuel D, Zigneco D, Reynes M, Feray C, Arulnaden JL, David MF, Gigou M, Bismuth A, Mathieu D, Gentilini P, Benhamou JP, Brechot C and Bismuth H. . 1995 Hepatology 21: 333–339.

  • Shridhar V, Siegfried J, Hunt J, Del Mar Alonso M and Smith DL. . 1994 Cancer Res. 54: 2084–2087.

  • Souza RF, Lei J, Yin J, Appel R, Zou TT, Zhou X, Wang S, Rhyu MG, Cymes K, Chan O, Park WS, Krasna MJ, Greenwald BD, Cottrell J, Abraham JM, Simms L, Leggett B, Young J, Harpaz N and Meltzer SJ. . 1997 Gastroenterol. 112: 40–45.

  • Tamura G, Sakata K, Maesawa C, Suzuki Y, Terashima M, Satoh K, Sekiyama S, Suzuki A, Eda Y and Stodate R. . 1995 Cancer Res. 55: 1933–1936.

  • Takenoshita S, Hagiware K, Gemma A, Nagashima M, Ryberg D, Lindstedt BA, Bennett WP, Haugen A and Harris CC. . 1997 Carcinogenesis 18: 1427–1429.

    Article  CAS  Google Scholar 

  • Thibodeau SN, Bren G and Schaid D. . 1993 Science 260: 816–819.

    Article  CAS  Google Scholar 

  • Togo G, Toda N, Kanai F, Kato N, Shiratori Y, Kishi K, Imazeki F, Makuuchi M and Omata M. . 1996 Cancer Res. 56: 5620–5623.

  • Uchida T, Wada C, Wang C, Egawa S, Ohtani H and Koshiba K. . 1994 Cancer Res. 54: 3682–3685.

  • Vincent F, Hagiwara K, Ke Y, Stoner GD, Demetrick DJ and Bennett WP. . 1996 Biochem. Biophys. Res. Commun. 223: 561–564.

  • Wada C, Shionoya S, Fujino Y, Tokuhiro H, Akahoshi T, Uchida T and Ohtani H. . 1994 Blood 83: 3449–3456.

  • Wooster R, Cleton-Janser, Collins N, Mangion J, Cormelis RS, Cooper CS, Gusterson BA, Ponderr BAJ, Von Deimling A, Wiestler OD, Cornelisse CJ, Devilee P and Stratton MR. . 1994 Nat. Genet. 6: 152–156.

  • Yeh SH, Chen PJ, Lai MY and Chen DS. . 1996 Gastroenterol. 110: 184–192.

  • Zborowska E, Kinzler KW, Vogelstein B, Brattain M and Wilson JKV. . 1995 Science 268: 1336–1338.

    Article  CAS  Google Scholar 

  • Zhu J, Guo SZ, Beggs AH, Maruyama T, Santarius T, Dashner K, Olsen N, Wu JK and Black P. . 1996 Oncogene 12: 1417–1423.

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Acknowledgements

We thank Dr E May for helpful advice and discussion and V Caillez for statistical analysis. This work was supported by grants from the Faculté de Médecine Paris-Sud.

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Salvucci, M., Lemoine, A., Saffroy, R. et al. Microsatellite instability in European hepatocellular carcinoma. Oncogene 18, 181–187 (1999). https://doi.org/10.1038/sj.onc.1202279

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