Lung Cancer
Volume 62, Issue 1 , Pages 120-125 , October 2008

Frequent p16 inactivation by homozygous deletion or methylation is associated with a poor prognosis in Japanese patients with pleural mesothelioma

  • Naruyuki Kobayashi

      Affiliations

    • Department of Cancer and Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan
  • ,
  • Shinichi Toyooka

      Affiliations

    • Department of Cancer and Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan
    • Corresponding Author InformationCorresponding author. Tel.: +81 86 235 7265; fax: +81 86 235 7269.
  • ,
  • Hiroyuki Yanai

      Affiliations

    • Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
  • ,
  • Junichi Soh

      Affiliations

    • Department of Cancer and Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan
  • ,
  • Nobukazu Fujimoto

      Affiliations

    • Department of Internal Medicine, Okayama Rosai Hospital, Okayama, Japan
  • ,
  • Hiromasa Yamamoto

      Affiliations

    • Department of Cancer and Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan
  • ,
  • Shuji Ichihara

      Affiliations

    • Department of Cancer and Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan
  • ,
  • Kentaro Kimura

      Affiliations

    • Department of Cancer and Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan
  • ,
  • Kouichi Ichimura

      Affiliations

    • Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
  • ,
  • Yoshifumi Sano

      Affiliations

    • Department of Cancer and Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan
  • ,
  • Takumi Kishimoto

      Affiliations

    • Department of Internal Medicine, Okayama Rosai Hospital, Okayama, Japan
  • ,
  • Hiroshi Date

      Affiliations

    • Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Japan

Received 14 December 2007 ,Revised 24 January 2008 ,Accepted 14 February 2008.

References 

  1. Robinson BW, Lake RA. Advances in malignant mesothelioma. N Engl J Med. 2005;353:1591–1603
  2. Lee AY, Raz DJ, He B, Jablons DM. Update on the molecular biology of malignant mesothelioma. Cancer. 2007;109:1454–1461
  3. Wagner JC, Sleggs CA, Marchand P. Diffuse pleural mesothelioma and asbestos exposure in the North Western Cape Province. Br J Ind Med. 1960;17:260–271
  4. Pass HI, Mitchell JB, Johnson DH, Turrisi AT, Minna JD. Lung cancer: principle and practice. Philadelphia: Lippincott Williams and Wilkins; 2000;p. 375–78
  5. Cheng JQ, Jhanwar SC, Klein WM, Bell DW, Lee WC, Altomare DA, et al. p16 alterations and deletion mapping of 9p21-p22 in malignant mesothelioma. Cancer Res. 1994;54:5547–5551
  6. Prins JB, Williamson KA, Kamp MM, Van Hezik EJ, Van der Kwast TH, Hagemeijer A, et al. The gene for the cyclin-dependent-kinase-4 inhibitor, CDKN2A, is preferentially deleted in malignant mesothelioma. Int J Cancer. 1998;75:649–653
  7. Illei PB, Rusch VW, Zakowski MF, Ladanyi M. Homozygous deletion of CDKN2A and codeletion of the methylthioadenosine phosphorylase gene in the majority of pleural mesotheliomas. Clin Cancer Res. 2003;9:2108–2113
  8. Merlo A, Herman JG, Mao L, Lee DJ, Gabrielson E, Burger PC, et al. 5’ CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancers. Nat Med. 1995;1:686–692
  9. Toyooka S, Pass HI, Shivapurkar N, Fukuyama Y, Maruyama R, Toyooka KO, et al. Aberrant methylation and simian virus 40 tag sequences in malignant mesothelioma. Cancer Res. 2001;61:5727–5730
  10. Wong L, Zhou J, Anderson D, Kratzke RA. Inactivation of p16INK4a expression in malignant mesothelioma by methylation. Lung Cancer. 2002;38:131–136
  11. Destro A, Ceresoli GL, Baryshnikova E, Garassino I, Zucali PA, De Vincenzo F, et al. Gene methylation in pleural mesothelioma: correlations with clinico-pathological features and patient's follow-up. Lung Cancer. 2007;
  12. Toyooka S, Maruyama R, Toyooka KO, McLerran D, Feng Z, Fukuyama Y, et al. Smoke exposure, histologic type and geography-related differences in the methylation profiles of non-small cell lung cancer. Int J Cancer. 2003;103:153–160
  13. Carbone M, Rizzo P, Grimley PM, Procopio A, Mew DJ, Shridhar V, et al. Simian virus-40 large-T antigen binds p53 in human mesotheliomas. Nat Med. 1997;3:908–912
  14. Aoe K, Hiraki A, Murakami T, Toyooka S, Shivapurkar N, Gazdar AF, et al. Infrequent existence of simian virus 40 large T antigen DNA in malignant mesothelioma in Japan. Cancer Sci. 2006;97:292–295
  15. Cristaudo A, Foddis R, Vivaldi A, Buselli R, Gattini V, Guglielmi G, et al. SV40 enhances the risk of malignant mesothelioma among people exposed to asbestos: a molecular epidemiologic case–control study. Cancer Res. 2005;65:3049–3052
  16. Tomii K, Tsukuda K, Toyooka S, Dote H, Hanafusa T, Asano H, et al. Aberrant promoter methylation of insulin-like growth factor binding protein-3 gene in human cancers. Int J Cancer. 2007;120:566–573
  17. Illei PB, Ladanyi M, Rusch VW, Zakowski MF. The use of CDKN2A deletion as a diagnostic marker for malignant mesothelioma in body cavity effusions. Cancer. 2003;99:51–56
  18. Herman JG, Graff JR, Myohanen S, Nelkin BD, Baylin SB. Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci USA. 1996;93:9821–9826
  19. Hirao T, Bueno R, Chen CJ, Gordon GJ, Heilig E, Kelsey KT. Alterations of the p16(INK4) locus in human malignant mesothelial tumors. Carcinogenesis. 2002;23:1127–1130
  20. Papp T, Schipper H, Pemsel H, Bastrop R, Muller KM, Wiethege T, et al. Mutational analysis of N-ras, p53, p16INK4a, p14ARF and CDK4 genes in primary human malignant mesotheliomas. Int J Oncol. 2001;18:425–433
  21. Xio S, Li D, Vijg J, Sugarbaker DJ, Corson JM, Fletcher JA. Codeletion of p15 and p16 in primary malignant mesothelioma. Oncogene. 1995;11:511–515
  22. Lopez-Rios F, Chuai S, Flores R, Shimizu S, Ohno T, Wakahara K, et al. Global gene expression profiling of pleural mesotheliomas: overexpression of aurora kinases and P16/CDKN2A deletion as prognostic factors and critical evaluation of microarray-based prognostic prediction. Cancer Res. 2006;66:2970–2979
  23. Borczuk AC, Taub RN, Hesdorffer M, Hibshoosh H, Chabot JA, Keohan ML, et al. P16 loss and mitotic activity predict poor survival in patients with peritoneal malignant mesothelioma. Clin Cancer Res. 2005;11:3303–3308
  24. Ladanyi M. Implications of P16/CDKN2A deletion in pleural mesotheliomas. Lung Cancer. 2005;49(Suppl. 1):S95–S98
  25. Robinson BW, Musk AW, Lake RA. Malignant mesothelioma. Lancet. 2005;366:397–408
  26. Frizelle SP, Grim J, Zhou J, Gupta P, Curiel DT, Geradts J, et al. Re-expression of p16INK4a in mesothelioma cells results in cell cycle arrest, cell death, tumor suppression and tumor regression. Oncogene. 1998;16:3087–3095
  27. Piperno-Neumann S, Oudar O, Reynier P, Briane D, Cao A, Jaurand MC, et al. Transfer into a mesothelioma cell line of tumor suppressor gene p16 by cholesterol-based cationic lipids. Biochim Biophys Acta. 2003;1611:131–139
  28. Sekido Y, Pass HI, Bader S, Mew DJ, Christman MF, Gazdar AF, et al. Neurofibromatosis type 2 (NF2) gene is somatically mutated in mesothelioma but not in lung cancer. Cancer Res. 1995;55:1227–1231
  29. Usami N, Fukui T, Kondo M, Taniguchi T, Yokoyama T, Mori S, et al. Establishment and characterization of four malignant pleural mesothelioma cell lines from Japanese patients. Cancer Sci. 2006;97:387–394
  30. Kratzke RA, Otterson GA, Lincoln CE, Ewing S, Oie H, Geradts J, et al. Immunohistochemical analysis of the p16INK4 cyclin-dependent kinase inhibitor in malignant mesothelioma. J Natl Cancer Inst. 1995;87:1870–1875
  31. Papp T, Schipper H, Pemsel H, Unverricht M, Muller KM, Wiethege T, et al. Mutational analysis of the PTEN/MMAC1 tumour suppressor gene in primary human malignant mesotheliomas. Oncol Rep. 2001;8:1375–1379

PII: S0169-5002(08)00074-3

doi: 10.1016/j.lungcan.2008.02.013

Lung Cancer
Volume 62, Issue 1 , Pages 120-125 , October 2008