Increased DNA methyltransferase expression in rhabdomyosarcomas.
In normal somatic cells, the methylation pattern of DNA is stably maintained by DNA (cytosine-5-)-methyltransferase (DNA methyltransferase). Increased expression of DNA methyltransferase has been detected in many types of human cancer and has been thought to play an important role in tumorigenesis. In our study, we developed a standardized reverse transcription-polymerase chain reaction (RT-PCR) assay to determine the mRNA levels of DNA methyltransferase in rhabdomyosarcoma, the most common soft tissue cancer in children. Using this assay, expression of DNA methyltransferase was analyzed for 32 rhabdomyosarcomas and 12 normal skeletal muscle samples. All tumor samples, of which 18 were embryonal and 14 were alveolar subtype, showed increased expression of DNA methyltransferase after normalization to beta-actin. Compared to normal skeletal muscle, the average increase of DNA methyltransferase expression was 6.7-fold (6.7 +/-()0.96) in the embryonal tumors and 3.7-fold (3.7 +/- 0.46) in the alveolar rhabdomyosarcomas. The difference in the average increase of the DNA methyltransferase expression was statistically significant in the 2 rhabdomyosarcoma subtypes, which have distinct etiologies and clinical behaviors. Our results are consistent with previous reports that an increase in DNA methyltransferase activity is associated with neoplastic transformation; however, the role of increased DNA methyltransferase expression in the development and progression of rhabdomyosarcoma needs to be investigated in future studies.
Chen
B
B
Department of Pathology, University of Arkansas for Medical Sciences and Arkansas Children's Hospital, Little Rock, AR 72202, USA. chenbin@exchange.uams.edu
Liu
X
X
Savell
V H
VH
Dilday
B R
BR
Johnson
M W
MW
Jenkins
J J
JJ
Parham
D M
DM
D000293:Adolescent; D019677:Artificial Gene Fusion; D002648:Child; D002675:Child, Preschool; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; D006801:Humans; D007150:Immunohistochemistry; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000201:enzymology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D000072041:PAX3 Transcription Factor; D051763:PAX7 Transcription Factor; D051761:Paired Box Transcription Factors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012208:Rhabdomyosarcoma / Q000201:enzymology* / Q000209:etiology; D014157:Transcription Factors / Q000378:metabolism
D004268:DNA-Binding Proteins; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051763:PAX7 Transcription Factor; D051761:Paired Box Transcription Factors; D014157:Transcription Factors; C068686:Pax3 protein, mouse; D004248:DNA (Cytosine-5-)-Methyltransferases