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Characterization of DNA hypermethylation in two cases of peritoneal mesothelioma

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Tumor Biology

Abstract

Malignant mesothelioma (MM) is a rare disease with a poor prognosis. Pleural mesothelioma, which is the most common type of MM, is considered to be caused by asbestos exposure and is increasing in incidence, with about 15,000 new cases diagnosed worldwide annually. On the other hand, peritoneal mesothelioma is a very rare type of MM; thus, its pathogenesis is even less understood than pleural mesothelioma. Recent research on the pathogenesis of malignant pleural mesothelioma has indicated that both epigenetic and genetic alterations contribute to tumorigenesis. Here, we hypothesize that peritoneal mesothelioma also has an epigenetic alteration in the same genes (Kazal-type serine peptidase inhibitor domain 1 (KAZALD1), transmembrane protein 30B (TMEM30B), and mitogen-activated protein kinase 13 (MAPK13)). Our goal is to identify DNA methylation of these three candidate genes in two peritoneal mesothelioma cases. Laser capture microdissection was used to separate diseased sections of formalin-fixed paraffin-embedded samples from one surgically resected tissue (epithelial type) and one autopsy tissue (sarcomatous type). Genomic DNA was subsequently extracted by the standard phenol chloroform method. The DNA was then treated with sodium bisulphite, and pyrosequencing analysis was used to quantitatively analyze the methylation of candidate genes reported to be hypermethylated in malignant pleural mesothelioma (KAZALD1, TMEM30B, and MAPK13). TMEM30B and MAPK13 were not methylated in either case. However, KAZALD1 was highly methylated in sarcomatoid-type peritoneal mesothelioma. We first report that the KAZALD1 gene was hypermethylated in sarcomatoid-type malignant peritoneal mesothelioma.

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Abbreviations

MM:

Malignant mesothelioma

MPM:

Malignant pleural mesothelioma

MPEM:

Malignant peritoneal mesothelioma

NF2:

Neurofibromatosis type 2

KAZALD1:

Kazal-type serine peptidase inhibitor domain 1

TMEM30B:

Transmembrane protein 30B

MAPK13:

Mitogen-activated protein kinase 13

PCR:

Polymerase chain reaction

CT:

Computed tomography

US:

Ultrasound

References

  1. Weiss SW, Tavassoli FA. Multicystic mesothelioma. An analysis of pathologic findings and biologic behavior in 37 cases. Am J Surg Pathol. 1988;12:737–46.

    Article  PubMed  CAS  Google Scholar 

  2. Ross MJ, Welch WR, Scully RE. Multilocular peritoneal inclusion cysts (so-called cystic mesotheliomas). Cancer. 1989;64:1336–46.

    Article  PubMed  CAS  Google Scholar 

  3. Barnetson RJ, Burnett RA, Downie I, Harper CM, Roberts F. Immunohistochemical analysis of peritoneal mesothelioma and primary and secondary serous carcinoma of the peritoneum: antibodies to estrogen and progesterone receptors are useful. Am J Clin Pathol. 2006;125:67–76.

    PubMed  CAS  Google Scholar 

  4. Briselli M, Mark EJ, Dickersin GR. Solitary fibrous tumors of the pleura: eight new cases and review of 360 cases in the literature. Cancer. 1981;47:2678–89.

    Article  PubMed  CAS  Google Scholar 

  5. Moertel CG. Peritoneal mesothelioma. Gastroenterology. 1972;63:346–50.

    PubMed  CAS  Google Scholar 

  6. Ito H, Imada T, Kondo J, et al. A case of malignant peritoneal mesothelioma showed complete remission with chemotherapy. Jpn J Clin Oncol. 1998;28:145–8.

    Article  PubMed  CAS  Google Scholar 

  7. Wagner JC, Sleggs CA, Marchand P. Diffuse pleural mesothelioma and asbestos exposure in the North Western Cape Province. Br J Ind Med. 1960;17:260–71.

    PubMed  CAS  Google Scholar 

  8. Spirtas R, Heineman EF, Bernstein L, et al. Malignant mesothelioma: attributable risk of asbestos exposure. Occup Environ Med. 1994;51:804–11.

    Article  PubMed  CAS  Google Scholar 

  9. Peto J, Hodgson JT, Matthews FE, Jones JR. Continuing increase in mesothelioma mortality in Britain. Lancet. 1995;345:535–9.

    Article  PubMed  CAS  Google Scholar 

  10. Peto J, Decarli A, La VC, Levi F, Negri E. The European mesothelioma epidemic. Br J Cancer. 1999;79:666–72.

    Article  PubMed  CAS  Google Scholar 

  11. Busch JM, Kruskal JB, Wu B. Best cases from the AFIP. Malignant peritoneal mesothelioma. Radiographics. 2002;22:1511–5.

    Article  PubMed  Google Scholar 

  12. Antman KH, Pomfret EA, Aisner J, MacIntyre J, Osteen RT, Greenberger JS. Peritoneal mesothelioma: natural history and response to chemotherapy. J Clin Oncol. 1983;1:386–91.

    PubMed  CAS  Google Scholar 

  13. Metintas S, Metintas M, Ucgun I, Oner U. Malignant mesothelioma due to environmental exposure to asbestos: follow-up of a Turkish cohort living in a rural area. Chest. 2002;122:2224–9.

    Article  PubMed  Google Scholar 

  14. Riddell RH, Goodman MJ, Moossa AR. Peritoneal malignant mesothelioma in a patient with recurrent peritonitis. Cancer. 1981;48:134–9.

    Article  PubMed  CAS  Google Scholar 

  15. Metcalf RA, Welsh JA, Bennett WP, et al. p53 and Kirsten-ras mutations in human mesothelioma cell lines. Cancer Res. 1992;52:2610–5.

    PubMed  CAS  Google Scholar 

  16. Kratzke RA, Otterson GA, Lincoln CE, et al. Immunohistochemical analysis of the p16INK4 cyclin-dependent kinase inhibitor in malignant mesothelioma. J Natl Cancer Inst. 1995;87:1870–5.

    Article  PubMed  CAS  Google Scholar 

  17. Cheng JQ, Jhanwar SC, Klein WM, et al. p16 alterations and deletion mapping of 9p21–p22 in malignant mesothelioma. Cancer Res. 1994;54:5547–51.

    PubMed  CAS  Google Scholar 

  18. Cote RJ, Jhanwar SC, Novick S, Pellicer A. Genetic alterations of the p53 gene are a feature of malignant mesotheliomas. Cancer Res. 1991;51:5410–6.

    PubMed  CAS  Google Scholar 

  19. Krasinskas AM, Bartlett DL, Cieply K, Dacic S. CDKN2A and MTAP deletions in peritoneal mesotheliomas are correlated with loss of p16 protein expression and poor survival. Mod Pathol. 2010;23:531–8.

    Article  PubMed  CAS  Google Scholar 

  20. Issa JP. CpG island methylator phenotype in cancer. Nat Rev Cancer. 2004;4:988–93.

    Article  PubMed  CAS  Google Scholar 

  21. Watanabe Y, Toyota M, Kondo Y, et al. PRDM5 identified as a target of epigenetic silencing in colorectal and gastric cancer. Clin Cancer Res. 2007;13:4786–94.

    Article  PubMed  CAS  Google Scholar 

  22. Issa JP, Ahuja N, Toyota M, Bronner MP, Brentnall TA. Accelerated age-related CpG island methylation in ulcerative colitis. Cancer Res. 2001;61:3573–7.

    PubMed  CAS  Google Scholar 

  23. Toyota M, Issa JP. CpG island methylator phenotypes in aging and cancer. Semin Cancer Biol. 1999;9:349–57.

    Article  PubMed  CAS  Google Scholar 

  24. Holliday R. The inheritance of epigenetic defects. Science. 1987;238:163–70.

    Article  PubMed  CAS  Google Scholar 

  25. Issa JP, Ottaviano YL, Celano P, Hamilton SR, Davidson NE, Baylin SB. Methylation of the oestrogen receptor CpG island links ageing and neoplasia in human colon. Nat Genet. 1994;7:536–40.

    Article  PubMed  CAS  Google Scholar 

  26. Hussain SP, Harris CC. Inflammation and cancer: an ancient link with novel potentials. Int J Cancer. 2007;121:2373–80.

    Article  PubMed  CAS  Google Scholar 

  27. Goto Y, Shinjo K, Kondo Y, et al. Epigenetic profiles distinguish malignant pleural mesothelioma from lung adenocarcinoma. Cancer Res. 2009;69:9073–82.

    Article  PubMed  CAS  Google Scholar 

  28. Gao W, Kondo Y, Shen L, et al. Variable DNA methylation patterns associated with progression of disease in hepatocellular carcinomas. Carcinogenesis. 2008;29:1901–10.

    Article  PubMed  CAS  Google Scholar 

  29. Hosoya K, Yamashita S, Ando T, Nakajima T, Itoh F, Ushijima T. Adenomatous polyposis coli 1A is likely to be methylated as a passenger in human gastric carcinogenesis. Cancer Lett. 2009;285:182–9.

    Article  PubMed  CAS  Google Scholar 

  30. Ushijima T. Epigenetic field for cancerization. J Biochem Mol Biol. 2007;40:142–50.

    Article  PubMed  CAS  Google Scholar 

  31. Toyota M, Ahuja N, Suzuki H, et al. Aberrant methylation in gastric cancer associated with the CpG island methylator phenotype. Cancer Res. 1999;59:5438–42.

    PubMed  CAS  Google Scholar 

  32. Oishi Y, Watanabe Y, Yoshida Y, et al. Hypermethylation of Sox17 gene is useful as a molecular diagnostic application in early gastric cancer. Tumour Biol. 2011;32:383–93.

    Google Scholar 

  33. Satoh A, Toyota M, Itoh F, et al. Epigenetic inactivation of CHFR and sensitivity to microtubule inhibitors in gastric cancer. Cancer Res. 2003;63:8606–13.

    PubMed  CAS  Google Scholar 

  34. Suzuki H, Watkins DN, Jair KW, et al. Epigenetic inactivation of SFRP genes allows constitutive WNT signaling in colorectal cancer. Nat Genet. 2004;36:417–22.

    Article  PubMed  CAS  Google Scholar 

  35. Suzuki H, Toyota M, Sato H, Sonoda T, Sakauchi F, Mori M. Roles and causes of abnormal DNA methylation in gastrointestinal cancers. Asian Pac J Cancer Prev. 2006;7:177–85.

    PubMed  Google Scholar 

  36. Suzuki H, Igarashi S, Nojima M, et al. IGFBP7 is a p53-responsive gene specifically silenced in colorectal cancer with CpG island methylator phenotype. Carcinogenesis. 2010;31:342–9.

    Article  PubMed  CAS  Google Scholar 

  37. Suzuki H, Yamamoto E, Nojima M, et al. Methylation-associated silencing of microRNA-34b/c in gastric cancer and its involvement in an epigenetic field defect. Carcinogenesis. 2010;31:2066–73.

    Article  PubMed  CAS  Google Scholar 

  38. Suzuki H, Itoh F, Toyota M, et al. Distinct methylation pattern and microsatellite instability in sporadic gastric cancer. Int J Cancer. 1999;83:309–13.

    Article  PubMed  CAS  Google Scholar 

  39. Toyota M, Ahuja N, Ohe-Toyota M, Herman JG, Baylin SB, Issa JP. CpG island methylator phenotype in colorectal cancer. Proc Natl Acad Sci U S A. 1999;96:8681–6.

    Article  PubMed  CAS  Google Scholar 

  40. Toyota M, Ho C, Ahuja N, et al. Identification of differentially methylated sequences in colorectal cancer by methylated CpG island amplification. Cancer Res. 1999;59:2307–12.

    PubMed  CAS  Google Scholar 

  41. Watanabe Y, Kim HS, Castoro RJ, et al. Sensitive and specific detection of early gastric cancer with DNA methylation analysis of gastric washes. Gastroenterology. 2009;136:2149–58.

    Article  PubMed  CAS  Google Scholar 

  42. Nakajima T, Enomoto S, Yamashita S, et al. Persistence of a component of DNA methylation in gastric mucosae after Helicobacter pylori eradication. J Gastroenterol. 2010;45:37–44.

    Article  PubMed  CAS  Google Scholar 

  43. Nakajima T, Yamashita S, Maekita T, Niwa T, Nakazawa K, Ushijima T. The presence of a methylation fingerprint of Helicobacter pylori infection in human gastric mucosae. Int J Cancer. 2009;124:905–10.

    Article  PubMed  CAS  Google Scholar 

  44. Nakajima T, Maekita T, Oda I, et al. Higher methylation levels in gastric mucosae significantly correlate with higher risk of gastric cancers. Cancer Epidemiol Biomarkers Prev. 2006;15:2317–21.

    Article  PubMed  CAS  Google Scholar 

  45. Maekita T, Nakazawa K, Mihara M, et al. High levels of aberrant DNA methylation in Helicobacter pylori-infected gastric mucosae and its possible association with gastric cancer risk. Clin Cancer Res. 2006;12:989–95.

    Article  PubMed  CAS  Google Scholar 

  46. Yamamoto E, Toyota M, Suzuki H, et al. LINE-1 hypomethylation is associated with increased CpG island methylation in Helicobacter pylori-related enlarged-fold gastritis. Cancer Epidemiol Biomarkers Prev. 2008;17:2555–64.

    Article  PubMed  CAS  Google Scholar 

  47. Baba S, Oishi Y, Watanabe Y, et al. Gastric wash-based molecular testing for antibiotic resistance in Helicobacter pylori. Digestion. 2011;84:299–305.

    Article  PubMed  CAS  Google Scholar 

  48. Nakajima T, Enomoto S, Ushijima T. DNA methylation: a marker for carcinogen exposure and cancer risk. Environ Health Prev Med. 2008;13:8–15.

    Article  PubMed  CAS  Google Scholar 

  49. Yamashita M, Toyota M, Suzuki H, et al. DNA methylation of interferon regulatory factors in gastric cancer and noncancerous gastric mucosae. Cancer Sci. 2010;101:1708–16.

    Article  PubMed  CAS  Google Scholar 

  50. Maruyama R, Akino K, Toyota M, et al. Cytoplasmic RASSF2A is a proapoptotic mediator whose expression is epigenetically silenced in gastric cancer. Carcinogenesis. 2008;29:1312–8.

    Article  PubMed  CAS  Google Scholar 

  51. Nojima M, Suzuki H, Toyota M, et al. Frequent epigenetic inactivation of SFRP genes and constitutive activation of Wnt signaling in gastric cancer. Oncogene. 2007;26:4699–713.

    Article  PubMed  CAS  Google Scholar 

  52. Akino K, Toyota M, Suzuki H, et al. Identification of DFNA5 as a target of epigenetic inactivation in gastric cancer. Cancer Sci. 2007;98:88–95.

    Article  PubMed  CAS  Google Scholar 

  53. Kubo T, Toyooka S, Tsukuda K, et al. Epigenetic silencing of microRNA-34b/c plays an important role in the pathogenesis of malignant pleural mesothelioma. Clin Cancer Res. 2011;17:4965–74.

    Article  PubMed  CAS  Google Scholar 

  54. Yoshikawa Y, Sato A, Tsujimura T, et al. Frequent inactivation of the BAP1 gene in epithelioid-type malignant mesothelioma. Cancer Sci. 2012;103:868–74.

    Article  PubMed  CAS  Google Scholar 

  55. Nishikawa H, Wu W, Koike A, et al. BRCA1-associated protein 1 interferes with BRCA1/BARD1 RING heterodimer activity. Cancer Res. 2009;69:111–9.

    Article  PubMed  CAS  Google Scholar 

  56. Vogelzang NJ, Rusthoven JJ, Symanowski J, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003;21:2636–44.

    Article  PubMed  CAS  Google Scholar 

  57. Murthy SS, Testa JR. Asbestos, chromosomal deletions, and tumor suppressor gene alterations in human malignant mesothelioma. J Cell Physiol. 1999;180:150–7.

    Article  PubMed  CAS  Google Scholar 

  58. Taguchi T, Jhanwar SC, Siegfried JM, Keller SM, Testa JR. Recurrent deletions of specific chromosomal sites in 1p, 3p, 6q, and 9p in human malignant mesothelioma. Cancer Res. 1993;53:4349–55.

    PubMed  CAS  Google Scholar 

  59. Balsara BR, Bell DW, Sonoda G, et al. Comparative genomic hybridization and loss of heterozygosity analyses identify a common region of deletion at 15q11.1–15 in human malignant mesothelioma. Cancer Res. 1999;59:450–4.

    PubMed  CAS  Google Scholar 

  60. Krismann M, Muller KM, Jaworska M, Johnen G. Molecular cytogenetic differences between histological subtypes of malignant mesotheliomas: DNA cytometry and comparative genomic hybridization of 90 cases. J Pathol. 2002;197:363–71.

    Article  PubMed  CAS  Google Scholar 

  61. Lee YC, Wang HP, Wang CP, et al. Revisit of field cancerization in squamous cell carcinoma of upper aerodigestive tract: better risk assessment with epigenetic markers. Cancer Prev Res (Phila). 2011;4:1982–92.

    Article  CAS  Google Scholar 

  62. Chan PS, Balfour TW, Bourke JB, Smith PG. Peritoneal nesothelioma. Br J Surg. 1975;62:576–80.

    Article  PubMed  CAS  Google Scholar 

  63. Kerrigan SA, Cagle P, Churg A. Malignant mesothelioma of the peritoneum presenting as an inflammatory lesion: a report of four cases. Am J Surg Pathol. 2003;27:248–53.

    Article  PubMed  Google Scholar 

  64. Ramaswamy G, Shah UB, Tchertkoff V. Diffuse malignant peritoneal mesothelioma presenting as acute appendicitis. N Y State J Med. 1984;84:125–7.

    PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported in part by The Japanese Foundation for Research and Promotion of Endoscopy (JFE) and The Japanese Society of Gastroenterology (JSGE) and The Princess Takamatsu Cancer Research Fund. Yoshiyuki Watanabe is a member of The Japan Gastroenterological Endoscopy Society (JGES) and the JSGE and is supported by a generous gift from both the JFE and the JSGE. The authors are grateful to Mr. Hiroyuki Nishikawa for his technical advice and Ms. Tina Butterfield for her critical advice.

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Authors and Affiliations

  1. School of Medicine, St. Marianna University School of Medicine, Kawasaki, Japan

    Ryota Hama, Kanako Shinada, Yosuke Yamada & Yuka Ogata

  2. Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan

    Yoshiyuki Watanabe, Yoshihito Yoshida, Tomohiro Tamura, Tetsuya Hiraishi, Ritsuko Oikawa, Tadateru Maehata & Fumio Itoh

  3. Department of Surgery, St. Marianna University School of Medicine, Kawasaki, Japan

    Jo Sakurai

  4. Department of Clinical Pathology, St. Marianna University School of Medicine, Kawasaki, Japan

    Tomohiro Tamura & Hirotaka Koizumi

  5. Department of Internal Medicine, Kawasaki Rinko General Hospital, Kawasaki, Japan

    Yoshiyuki Watanabe & Yoshihito Yoshida

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  1. Ryota Hama
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Correspondence to Yoshiyuki Watanabe.

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Ryota Hama and Yoshiyuki Watanabe contributed equally to this work.

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Supplementary Table 1

Primers and PCR conditions (DOC 99 kb)

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Hama, R., Watanabe, Y., Shinada, K. et al. Characterization of DNA hypermethylation in two cases of peritoneal mesothelioma. Tumor Biol. 33, 2031–2040 (2012). https://doi.org/10.1007/s13277-012-0462-8

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  • DOI: https://doi.org/10.1007/s13277-012-0462-8

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