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WT1 probe for FISH CE/IVD - Salivary gland cancers
The WT1 gene is located on 11p13 and encodes a zinc finger DNA-binding protein that acts as a transcriptional activator or repressor depending on the cellular or chromosomal context. Inactivating mutations in the tumor suppressor gene WT1 have been identified in patients with Wilms' tumor and in a subset of sporadic cancers. However, in desmoblastic small round cell tumors (DSRCT) recurrent translocations affecting the WT1 gene have been found. DSRCT is a highly aggressive mesenchymal tumor that primarily affects male adolescents and young adults. The translocation t(11;22)(p13;q12.2) is detectable in virtually all DSRCT tested and results in the fusion of the potent transcriptional activator domain of the EWSR1 gene and the DNA-binding zinc-finger domains of the WT1 gene. The EWSR1-WT1 chimeric protein acts as an oncogenic transcription factor as evidenced by its ability to transform cells in vitro. While EWSR1 rearrangements are present in about 90% of DSRCT but are also frequently found in other small round blue cell neoplasms as e.g. Ewing sarcoma, WT1 translocations are exclusively found in DSRCT. Hence, detection of the t(11;22) by Fluorescence in situ Hybridization represents a valuable tool for the differential diagnosis of DSRCT.
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