[1958] Characterisation of t(10;17)(q22;p13) in Clear Cell Sarcoma of Kidney

Elaine O'Meara, Deirdre Stack, Cheng-Han Lee, Jerry Garvin, Tom Morris, Pedram Argani, David Gisselsson, Ivo Leuschner, Manfred Gessler, Norbert Graf, Jonathan A Fletcher, Maureen J O'Sullivan. Our Lady's Children's Hospital, Crumlin, Dublin, Ireland

Background: Clear cell sarcoma of kidney [CCSK], the second commonest pediatric renal cancer is classified as unfavorable histology by the National Wilms Tumor Study group. It is diagnostically challenging, therapy-resistant and has poor outcomes. Nothing is currently known about CCSK biology. Array CGH has shown no consistent genomic aberrations. Three case reports of CCSK with balanced translocation t(10;17)(p13;q22), prompted our investigation into t(10:17), to identify the genes involved and establish translocation incidence.
Design: 51 CCSKs were sourced from Europe and North America, touch imprints for fluorescence in-situ hybridisation [FISH] made and RNA extracted. The breakpoints on chromosomes 10 and 17 were identified in the index case with t(10;17)(q22;p13), using fluorescently labelled BACs. RT-PCR with primers specific for candidate genes within the breakpoint regions was carried out to identify the fusion transcript in the index case and the product sequenced. The 50 CCSKs were screened by FISH and RT-PCR for evidence of the translocation/transcript.

Results: t(10:17)(q22;p13) in CCSK involves YWHAE on chromosome 17 and members of the FAM22 gene family on chromosome 10. Exons 1-5 of YWHAE are fused in-frame to exons 2-7 of FAM22 genes. The YWHAE-FAM22 fusion transcript was identified in 7 of 51 CCSK cases, 12% of the total cases tested. Clinico-morphological correlates of translocation status were investigated and significant differences in tumor stage and cellularity noted between transcript-positive and transcript-negative cases.
Conclusions: Identification of the genes involved in CCSK-associated t(10:17) represents the first step in understanding CCSKmolecular genetics. Although the proportion of cases with the translocation is relatively low [12%], it is possible that the involved genes are dysregulated by alternative means in transcript-negative cases. There was a significant difference in stage of transcript-positive versus -negative cases with no transcript-positive case presenting with stage I disease, despite this representing 31% of cases. No significant differences in outcome were detectable between transcript-positive and transcript-negative cases. We are now studying the cell biological effects of expressing this transcript.
Category: Pediatrics

Monday, March 19, 2012 11:30 AM

Platform Session: Section H, Monday Morning


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