title: Characterization of DNA hypermethylation in two cases of peritoneal mesothelioma.
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.
authors: School of Medicine, St Marianna University School of Medicine, Kawasaki, Japan.
authors: Ryota
authors: R
authors: Hama
authors: Yoshiyuki
authors: Y
authors: Watanabe
authors: Kanako
authors: K
authors: Shinada
authors: Yosuke
authors: Y
authors: Yamada
authors: Yuka
authors: Y
authors: Ogata
authors: Yoshihito
authors: Y
authors: Yoshida
authors: Tomohiro
authors: T
authors: Tamura
authors: Tetsuya
authors: T
authors: Hiraishi
authors: Ritsuko
authors: R
authors: Oikawa
authors: Jo
authors: J
authors: Sakurai
authors: Tadateru
authors: T
authors: Maehata
authors: Hirotaka
authors: H
authors: Koizumi
authors: Fumio
authors: F
authors: Itoh
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008654:Mesothelioma / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D048292:Mitogen-Activated Protein Kinase 13 / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010534:Peritoneal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D010997:Pleural Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D012509:Sarcoma / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D015842:Serine Proteinase Inhibitors / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D018631:ras Proteins / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C117307:KRAS protein, human; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D015842:Serine Proteinase Inhibitors; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D048292:Mitogen-Activated Protein Kinase 13; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins