PURPOSE: Testicular germ cell tumors (TGCT) have a unique epigenetic profile 
distinct from that of other types of cancer. Elucidation of these properties has 
a potential to identify novel markers for TGCTs.
EXPERIMENTAL DESIGN: We conducted comprehensive analysis of DNA 
methyltransferase (DNMT) gene expression in TGCTs. Based on the expression 
profiles of DNMT genes in TGCTs, we generated a rabbit polyclonal anti-human 
DNMT3L antibody. We then studied the role of DNMT3L in TGCTs by the treatment of 
two embryonal carcinoma (EC) cell lines with a small interfering RNA system. 
Finally, we evaluated the immunohistochemical detection of DNMT3L in TGCT 
tissues. We also compared the patterns of DNMT3L immunohistochemistry with those 
of CD30 and SOX2.
RESULTS: Among the DNMT genes, we found that mRNA for DNMT3L was specifically 
expressed in TGCTs, but neither in normal testicular tissues nor in cancer cells 
of somatic tissue origin. DNMT3L protein was strongly expressed in two EC cell 
lines, but not in the cell lines of somatic tissue origin. Transfection of small 
interfering RNA for DNMT3L significantly reduced DNMT3L expression and resulted 
in growth suppression and apoptosis in EC cells. Immunohistochemical analysis 
showed that DNMT3L protein was present only in EC cells, but not in the other 
types of TGCT components and cancer cells of somatic tissue origin. DNMT3L 
staining was more prominent and specific than CD30 or SOX2 staining for 
detecting EC cells.
CONCLUSION: DNMT3L is a novel marker and is essential for the growth of human 
embryonal carcinoma.