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The CpG island of the novel tumor suppressor gene RASSF1A is intensely methylated in primary small cell lung carcinomas

Oncogene volume 20, pages 3563–3567 (2001)Cite this article

Abstract

Loss of heterozygosity at 3p21.3 occurs in more than 90% of small cell lung carcinomas (SCLCs). The Ras association domain family 1 (RASSF1) gene cloned from the lung tumor suppressor locus 3p21.3 consists of two major alternative transcripts, RASSF1A and RASSF1C. Epigenetic inactivation of isoform A (RASSF1A) was observed in 40% of primary non-small cell lung carcinomas and in several tumor cell lines. Transfection of RASSF1A suppressed the growth of lung cancer cells in vitro and in nude mice. Here we have analysed the methylation status of the CpG island promoters of RASSF1A and RASSF1C in primary SCLCs. In 22 of 28 SCLCs (=79%) the promoter of RASSF1A was highly methylated at all CpG sites analysed. None of the SCLCs showed evidence for methylation of the CpG island of RASSF1C. The results suggest that hypermethylation of the CpG island promoter of the RASSF1A gene is associated with SCLC pathogenesis.

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References

  • Antequera F, Boyes J, Bird A . 1990 Cell 62: 503–514

  • Bar-Sagi D, Feramisco JR . 1985 Cell 42: 841–848

  • Baylin SB, Herman JG . 2000 Trends Genet. 16: 168–174

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

  • Belinsky SA, Nikula KJ, Palmisano WA, Michels R, Saccomanno G, Gabrielson E, Baylin SB, Herman JG . 1998 Proc. Natl. Acad. Sci. USA 95: 11891–11896

  • Chen CY, Liou J, Forman LW, Faller DV . 1998 J. Biol. Chem. 273: 16700–16709

  • Clark SJ, Harrison J, Paul CL, Frommer M . 1994 Nucleic Acids Res. 22: 2990–2997

  • Dammann R, Li C, Yoon JH, Chin PL, Bates S, Pfeifer GP . 2000 Nature Genet. 25: 315–319

  • Downward J . 1998 Curr. Opin. Genet. Dev. 8: 49–54

  • Girard L, Zochbauer-Muller S, Virmani AK, Gazdar AF, Minna JD . 2000 Cancer Res. 60: 4894–4906

  • Hibi K, Takahashi T, Yamakawa K, Ueda R, Sekido Y, Ariyoshi Y, Suyama M, Takagi H, Nakamura Y . 1992 Oncogene 7: 445–449

  • Hung J, Kishimoto Y, Sugio K., Virmani A, McIntire DD, Minna JD, Gazdar AF . 1995 JAMA 273: 558–563

  • Jones PA, Wolkowicz MJ, Rideout WM, Gonzales FA, Marziasz CM, Coetzee GA, Tapscott SJ . 1990 Proc. Natl. Acad. Sci. USA 87: 6117–6121

  • Jones PA, Laird PW . 1999 Nature Genet. 21: 163–167

  • Killary AM, Wolf ME, Giambernardi TA, Naylor SL . 1992 Proc. Natl. Acad. Sci. USA 89: 10877–10881

  • Kohno T, Yokota J . 1999 Carcinogenesis 20: 1403–1410

  • Kok K, Naylor SL, Buys CHCM . 1997 Adv. Cancer Res. 71: 27–92

  • Lerman MI, Minna JD . 2000 Cancer Res. 60: 6116–6133

  • Lindblad-Toh K, Tanenbaum DM, Daly MJ, Winchester E, Lui WO, Villapakkam A, Stanton SE, Larsson C, Hudson TJ, Johnson BE, Lander ES, Meyerson M . 2000 Nature Biotechnol. 18: 1001–1005

  • Mayo MW, Wang CY, Cogswell PC, Rogers-Graham KS, Lowe SW, Der CJ, Baldwin Jr. AS . 1997 Science 278: 1812–1815

  • Merlo A, Herman JG, Mao L, Lee DJ, Gabrielson E, Burger PC, Baylin SB, Sidransky D . 1995 Nature Med. 1: 686–692

  • Mitsudomi T, Viallet J, Mulshine JL, Linnoila RI, Minna JD., Gazdar AF . 1991 Oncogene 6: 1353–1362

  • Naylor SL, Johnson BE, Minna JD, Sakaguchi AY . 1987 Nature 329: 451–454

  • Otterson GA, Khleif SN, Chen W, Coxon AB, Kaye FJ . 1995 Oncogene 11: 1211–1216

  • Palmisano WA, Divine KK, Saccomanno G, Gilliland FD, Baylin SB, Herman JG, Belinsky SA . 2000 Cancer Res. 60: 5954–5958

  • Sekido Y, Ahmadian M, Wistuba II, Latif F, Bader S, Wei M-H, Duh F-M, Gazdar AF, Lerman MI, Minna JD . 1998 Oncogene 16: 3151–3157

  • Serrano, M, Lin AW, McCurrach ME, Beach D, Lowe SW . 1997 Cell 88: 593–602

  • Shao J, Sheng H, DuBois RN, Beauchamp RD . 2000 J. Biol. Chem. 275: 22916–22924

  • Shapiro GI, Park JE, Edwards CD, Mao L, Merlo A, Sidransky D, Ewen ME, Rollins BJ . 1995 Cancer Res. 55: 6200–6209

  • Sundaresan V, Ganly P, Hasleton P, Rudd R, Sinha G, Bleehen N, Rabbitts P . 1992 Oncogene 7: 1989–1997

  • Tang X, Khuri FR, Lee JJ, Kemp BL, Liu D, Hong WK, Mao L . 2000 J. Natl. Cancer Inst. 92: 1511–1516

  • Thiberville, L, Payne P, Vielkinds J, LeRiche J, Horsman D, Nouvet G, Palcic B, Lam S . 1995 Cancer Res. 55: 5133–5139

  • Todd S, Franklin WA, Varella-Garcia M, Kennedy T, Hilliker Jr CE, Hahner L, Anderson M, Wiest JS, Drabkin HA, Gemmill RM . 1997 Cancer Res. 57: 1344–1352

  • Vavvas D, Li X, Avruch J, Zhang X-F . 1998 J. Biol. Chem. 273: 5439–5442

  • Vos MD, Ellis CA, Bell A, Birrer MJ, Clark GJ . (2000). J. Biol. Chem. 275: 35669–35672

  • Wagner SN, Muller R, Boehm J, Putz B, Wunsch PH, Hofler H . 1993 Virchows Arch. B 63 325–329

  • Wei M-H, Latif F, Bader S, Kashuba V, Chen J-Y, Duh F-M, Sekido Y, Lee C-C, Geil L, Kuzmin I, Zabarovsky E, Klein G, Zbar B, Minna JD, Lerman MI . 1996 Cancer Res. 56: 1487–1492

  • Whang-Peng J, Kao-Shan CS, Lee EC, Bunn PA, Carney DN, Gazdar AF, Minna JD . 1982 Science 215: 181–182

  • Wingo PA, Ries LA, Giovino GA, Miller DS, Rosenberg HM, Shopland DR, Thun MJ, Edwards BK . 1999 J. Natl. Cancer Inst., 91: 675–690

  • Wistuba II., Behrens C, Milchgrub S, Bryant D, Hung J, Minna JD, Gazdar AF . 1999 Oncogene 18: 643–650

  • Wistuba II, Behrens C, Virmani AK, Mele G, Milchgrub S, Girard L, Fondon III, JW, Garner HR, McKay B, Latif F, Lerman MI, Lam S, Gazdar AF, Minna JD . 2000 Cancer Res. 60: 1949–1960

  • Wu W, Kemp BL, Proctor ML, Gazdar AF, Minna JD, Hong WK, Mao L . 1999 Cancer Res. 59: 1846–1851

  • Xiong Z, Laird PW . 1997 Nucleic Acids Res. 25: 2532–2534

  • Yamakawa K, Takahashi T, Horio Y, Murata Y, Takahashi E, Hibi K, Yokoyama S, Ueda R, Nakamura Y . 1993 Oncogene 8: 327–330

  • Yatabe Y, Konishi H, Mitsudomi T, Nakamura S, Takahashi T . 2000 Am. J. Pathol. 157: 985–993

  • Yokota J, Wada M, Shimosato Y, Terada M, Sugimura T . 1987 Proc. Natl. Acad. Sci. USA 84: 9252–9256

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Acknowledgements

This work was supported by a grant from the University of California Tobacco Related Disease Research Program (9RT-0175) to GP Pfeifer.

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Authors and Affiliations

  1. Department of Biology, Beckman Research Institute, City of Hope Cancer Center, Duarte, 91010, California, USA

    Reinhard Dammann & Gerd P Pfeifer

  2. Division of Molecular Oncology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan

    Takashi Takahashi

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Dammann, R., Takahashi, T. & Pfeifer, G. The CpG island of the novel tumor suppressor gene RASSF1A is intensely methylated in primary small cell lung carcinomas. Oncogene 20, 3563–3567 (2001). https://doi.org/10.1038/sj.onc.1204469

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