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Molecular variants of the EWS-WT1 gene fusion in desmoplastic small round cell tumor
C R Antonescu1, W L Gerald, M S Magid
1Department of Pathology, Human Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Abstract:
We report two cases of desmoplastic small round cell tumor (DSRCT) with novel molecular variants of the specific EWS-WT1 gene fusion. This fusion usually encodes a chimeric RNA with an in-frame junction of exon 7 of EWS to exon 8 of WT1. In one variant patient, the EWS-WT1 fusion transcript contained an in-frame junction of exon 9 of EWS to exon 8 of WT1. Moreover, in this patient the tumor arose in the hand, an extremely unusual site for DSRCT. In the second patient, an in-frame junction of exon 10 of EWS to exon 8 of WT1 was present. These two cases of DSRCT show that the molecular variability in the EWS breakpoint observed in the EWS-FLI1 fusion of Ewing's sarcoma can occur in DSRCT as well. This type of heterogeneity is relevant to the interpretation of molecular diagnostic assays and could also affect the functional properties of the encoded chimeric transcription factors.
Insights
Two desmoplastic small round cell tumor (DSRCT) cases reveal new EWS-WT1 gene fusion variants. This molecular diversity, including unusual tumor sites, impacts diagnostic interpretation and understanding of DSRCT.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Desmoplastic small round cell tumor (DSRCT) is a rare and aggressive cancer.
- The characteristic molecular hallmark of DSRCT is the EWS-WT1 gene fusion.
- This fusion typically results in a chimeric RNA with an in-frame junction of EWS exon 7 to WT1 exon 8.
Observation:
- Two DSRCT cases presented with previously undescribed molecular variants of the EWS-WT1 gene fusion.
- One patient exhibited an EWS exon 9 to WT1 exon 8 in-frame junction, with the tumor located in the hand, an atypical site for DSRCT.
- The second patient showed an EWS exon 10 to WT1 exon 8 in-frame junction.
Findings:
- These findings demonstrate molecular heterogeneity in the EWS breakpoint of DSRCT, mirroring variability seen in Ewing's sarcoma (EWS-FLI1 fusion).
- The identified EWS-WT1 fusion variants involve different exons of the EWS gene, leading to novel chimeric transcripts.
- The occurrence of DSRCT in an unusual anatomical location (hand) in one case is noteworthy.
Implications:
- The observed molecular variability in DSRCT is crucial for the accurate interpretation of molecular diagnostic assays.
- These novel gene fusion variants may influence the functional properties and oncogenic potential of the resulting chimeric transcription factors.
- Understanding this heterogeneity can inform future therapeutic strategies and prognostic assessments for DSRCT patients.