Aberrant methylation of tumour-related genes in thymic epithelial tumours.
BACKGROUND
Thymoma is an uncommon neoplasm derived from epithelial cells of the thymus. Few studies have addressed the genetic alterations that occur in the tumourigenesis of thymoma.


METHODS
We examined aberrant DNA methylation of DAP-K, p-16, MGMT and HPP1 genes in 26 thymomas and 6 thymic carcinoma to clarify the association between aberrant DNA methylation and clinicopathological features.


RESULTS
Fifteen (47%) of 32 thymic epithelial tumours showed aberrant methylation. Aberrant methylation was more frequent in thymic carcinoma (86%) than in thymoma (29%). Moreover, the frequency of tumours with methylation of multiple genes in thymic carcinoma was higher than in thymoma (60% vs 20%). In thymoma, the frequency of tumour methylation, including the type A tumour component (28%), was lower than that of tumours with type B tumour component (42%). MGMT methylation was detected in 23% of thymoma and in 83% of thymic carcinoma. The frequency of methylation of the MGMT gene in both tumours was high compared with the other 3 genes.


CONCLUSIONS
Aberrant DNA methylation was more frequent in thymic carcinoma than in thymoma, and the frequency of DNA methylation in thymic epithelial tumours is roughly parallel to their malignant behaviour.
Hirose
Yukiko
Y
Department of Oncological and Regenerative Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Japan.
Kondo
Kazuya
K
Takizawa
Hiromitsu
H
Nagao
Taeko
T
Nakagawa
Yasushi
Y
Fujino
Haruhiko
H
Toba
Hiroaki
H
Kenzaki
Koichiro
K
Sakiyama
Shoji
S
Tangoku
Akira
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology*; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D064550:Death-Associated Protein Kinases; D005260:Female; D019942:Genes, p16; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D013945:Thymoma / Q000235:genetics* / Q000473:pathology*; D013953:Thymus Neoplasms / Q000235:genetics* / Q000473:pathology*; D025521:Tumor Suppressor Proteins / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C423567:TMEFF2 protein, human; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D045643:DNA Repair Enzymes