Tumor Biology

, Volume 33, Issue 6, pp 2031–2040

Characterization of DNA hypermethylation in two cases of peritoneal mesothelioma

  • Ryota Hama
  • Yoshiyuki Watanabe
  • Kanako Shinada
  • Yosuke Yamada
  • Yuka Ogata
  • Yoshihito Yoshida
  • Tomohiro Tamura
  • Tetsuya Hiraishi
  • Ritsuko Oikawa
  • Jo Sakurai
  • Tadateru Maehata
  • Hirotaka Koizumi
  • Fumio Itoh
Research Article

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.

Keywords

Mesothelioma DNA methylation Peritoneal 

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

Supplementary material

13277_2012_462_MOESM1_ESM.doc (99 kb)
Supplementary Table 1Primers and PCR conditions (DOC 99 kb)

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2012

Authors and Affiliations

  • Ryota Hama
    • 1
  • Yoshiyuki Watanabe
    • 2
    • 5
  • Kanako Shinada
    • 1
  • Yosuke Yamada
    • 1
  • Yuka Ogata
    • 1
  • Yoshihito Yoshida
    • 2
    • 5
  • Tomohiro Tamura
    • 2
    • 4
  • Tetsuya Hiraishi
    • 2
  • Ritsuko Oikawa
    • 2
  • Jo Sakurai
    • 3
  • Tadateru Maehata
    • 2
  • Hirotaka Koizumi
    • 4
  • Fumio Itoh
    • 2
  1. 1.School of MedicineSt. Marianna University School of MedicineKawasakiJapan
  2. 2.Division of Gastroenterology and Hepatology, Department of Internal MedicineSt. Marianna University School of MedicineKawasakiJapan
  3. 3.Department of SurgerySt. Marianna University School of MedicineKawasakiJapan
  4. 4.Department of Clinical PathologySt. Marianna University School of MedicineKawasakiJapan
  5. 5.Department of Internal MedicineKawasaki Rinko General HospitalKawasakiJapan

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