title: Methylation and expression profiles of MGMT gene in thymic epithelial tumors.
abstract: OBJECTIVE
  A key challenge in diagnosis and treatment of thymic epithelial tumors (TET) is in improving our understanding of the genetic and epigenetic changes of these relatively rare tumors.
  
  
  METHODS
  Methylation specific PCR (MSP) and immunohistochemistry were applied to 66 TET to profile the methylation status of DNA repair gene O6-methylguanine DNA methyltransferase (MGMT) and its protein expression in TET to clarify the association between MGMT status and clinicopathological features, response to chemotherapy and overall survival.
  
  
  RESULTS
  MGMT methylation was significantly more frequent in thymic carcinoma than in thymoma (17/23, 74% versus 13/44, 29%; P<0.001). Loss of expression of MGMT protein was significantly more frequent in thymic carcinoma than in thymoma (20/23, 87% versus 10/44, 23%; P<0.0001). There is a significant correlation between of MGMT methylation and loss of its protein expression (P<0.0003). MGMT methylation and loss of expression were significantly more frequent in advanced thymic epithelial tumors (III/IV) than in early tumors (I/II).
  
  
  CONCLUSIONS
  MGMT methylation plays a soul role in development of TET, especially in thymic carcinoma. Therefore, translation of our results from basic molecular research to clinical practice may have important implication for considering MGMT methylation as a marker and a target of future therapies in TET.
authors.affiliation: Department of Oncological Medical Services, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan; Department of Oncological Surgery, Minia Oncology Institute, Minia, Egypt.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Mokhtar
authors.affiliation: Department of Oncological Medical Services, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan. Electronic address: kondo@clin.med.tokushima-u.ac.jp.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kondo
authors.affiliation: Department of Oncological Medical Services, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Namura
authors.affiliation: Department of Respiratory Medicine, Sohag Faculty of Medicine, Sohag University, Sohag, Egypt.
authors.forename: Abdellah H K
authors.initials: AH
authors.lastname: Ali
authors.affiliation: Department of Oncological Medical Services, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Yui
authors.initials: Y
authors.lastname: Fujita
authors.affiliation: Department of Oncological Medical Services, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Chikako
authors.initials: C
authors.lastname: Takai
authors.affiliation: Department of Thoracic, Endocrine and Oncological Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Takizawa
authors.affiliation: Department of Thoracic, Endocrine and Oncological Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Nakagawa
authors.affiliation: Department of Thoracic, Endocrine and Oncological Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Toba
authors.affiliation: Department of Thoracic, Endocrine and Oncological Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Kajiura
authors.affiliation: Department of Thoracic, Endocrine and Oncological Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Mitsuteru
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: Department of Thoracic, Endocrine and Oncological Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Gyokei
authors.initials: G
authors.lastname: Kawakami
authors.affiliation: Department of Thoracic, Endocrine and Oncological Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Sakiyama
authors.affiliation: Department of Thoracic, Endocrine and Oncological Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Tangoku
mesh_terms: D000328:Adult; D000368:Aged; D063646:Carcinogenesis / Q000235:genetics; D002277:Carcinoma / Q000235:genetics / Q000401:mortality; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D044127:Epigenesis, Genetic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000401:mortality; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013945:Thymoma / Q000235:genetics* / Q000401:mortality; D013953:Thymus Neoplasms / Q000235:genetics* / Q000401:mortality; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes
keywords: DNA methylation; Gene silencing; M; MG; MGMT; MI; MSP; NI; O(6)-methylguanine DNA methyltransferase; O(6)-methylguanine-DNA methyltransferase; TET; Thymic carcinoma; Thymic epithelial tumors; Thymoma; U; WHO; World Health Organization; methylated; methylation index; methylation-specific PCR; myasthenia gravis; non-informative case; thymic epithelial tumors; unmethylated