To further elucidate the significance of alterations in the Shh signaling pathway, we investigated 31 sporadic BCCs and 15 PNETs for the mutation and/or expression of SMOH, PTCH, SHH, and GL11.
To further elucidate the significance of alterations in the Shh signaling pathway, we investigated 31 sporadic BCCs and 15 PNETs for the mutation and/or expression of SMOH, PTCH, SHH, and GL11.
In conclusion, the detection of t(11;22) and EWS/FLI-1 fusion transcripts is considered to provide a novel adjunctive method for diagnosing renal PNET.
Ewing's sarcoma (ES) and primitive neuroectodermal tumor (PNET) are members of a tumor family consistently associated with chromosomal translocation and functional fusion of the EWS gene to any of several structurally related transcription factor genes.
EWS-Fli1, a fusion gene resulting from the chromosomal translocation t(11;22, q24;q12), encodes a transcriptional activator, promotes cellular transformation, and is often found in Ewing sarcoma and primitive neuroectodermal tumor.
Fluorescence in situ hybridization analysis of paraffin-embedded tissue revealed that three of four tumors were positive for a chromosomal translocation involving the EWS locus at 22q12, seen in more than 90% of cases of Ewing's sarcoma/malignant primitive neuroectodermal tumor.One case was not analyzable.
We found disagreement in only three samples: one ES/pPNET and one embryonal rhabdomyosarcoma harbor a PAX3-FOXO1 translocation (for ARMS), and one neuroepithelioma harboring a EWS-WT1 (for DSRCT).
The t(11;22) chromosomal translocation specifically linked to Ewing sarcoma and primitive neuroectodermal tumor results in a chimeric molecule fusing the amino-terminus-encoding region of the EWS gene to the carboxyl-terminal DNA-binding domain encoded by the FLI-1 gene.
The chimeric gene EWS/FLI-1, the hallmark of the Ewing's sarcoma and primitive neuroectodermal tumor family, encodes a fusion protein with enhanced transcriptional activation properties and preserved recognition of canonical ETS binding sites.
These results suggest that EWS-Fli1 may play an important role in the proliferation of the tumor cells, and the EWS-Fli1 fusion RNA could be used as a target to inhibit the growth of Ewing's sarcoma and primitive neuroectodermal tumor with the specific antisense oligonucleotide.
EWSR1 FISH was sensitive among high-grade round cell sarcomas (positive in 100% of desmoplastic small round cell tumors and 96% of Ewing sarcoma/primitive neuroectodermal tumors) but not specific because clear cell sarcoma, extraskeletal myxoid chondrosarcoma, and a subset of round cell liposarcomas also harbor rearrangements of EWSR1.
Molecular testing demonstrated the expression of EWS/FLI1 fusion transcripts corresponding to the t(11;22)(q24;q12) translocation, which confirmed the diagnosis of PNET of the uterine cervix.