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Example sentences for: gcts
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NSGCTs display complex differentiation patterns that include embryonal, extra-embryonal, and somatic tissue types [ 6 ] . Teratomas with somatic differentiation can undergo additional malignant transformation with characteristics of epithelial, mesenchymal, neurogenic, or hematologic tumors [ 7 ] . While the majority of GCTs exhibit exquisite sensitivity to cisplatin-based chemotherapy, a small proportion of metastatic tumors remain resistant.
A unique feature of GCTs is their origin from germ cells at a stage in development where they undergo epigenetic reprogramming [ 6 13 ] . The absence of this epigenetic modification in SGCTs is consistent with their GC-like nature as previously noted [ 6 14 ] . On the other hand, the extensive promoter hypermethylation seen in NSGCTs suggests a mechanistic role in their potential for embryonal and extra-embryonal lineage differentiation [ 6 14 ] . Establishment of DNA methylation in the mammalian genome is controlled by at least three DNA methyltransferases (DNMTs), DNMT1 , DNMT3a and DNMT3b [ 15 ] . The role of these DNMTs in differential de novo methylation in SGCT vs.
It has been shown that engineered over-expression of wild-type p53 in vitro causes inhibition of MGMT transcription in human tumor cells [ 29 ] . Abundant over-expression of wild-type p53, owing to their stage of origin, is a characteristic feature of GCTs [ 30 ] . A possibility also exists that the MGMT expression may, in general, be down regulated in tumors arising from embryonic-type cells.
Given the importance of the MGMT protein in treatment response to alkylating agents, this molecular switch may play a critical role in sensitivity to cisplatin-based therapy in GCTs.
Thus in these cases, promoter hypermethylation is one mechanism whereby gene expression can be deregulated in GCTs.
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