title: Characterization of the chromosomal translocation t(10;17)(q22;p13) in clear cell sarcoma of kidney.
abstract: Clear cell sarcoma of kidney (CCSK) is classified as a tumour of unfavourable histology by the National Wilms' Tumor Study Group. It has worse clinical outcomes than Wilms' tumour. Virtually nothing is known about CCSK biology, as there have been very few genetic aberrations identified to act as pointers in this cancer. Three cases of CCSK bearing a chromosomal translocation, t(10;17)(q22;p13), have been individually reported but not further investigated to date. The aim of this research was to characterize t(10;17)(q22;p13) in CCSK to identify the genes involved in the translocation breakpoints. Using fluorescently labelled bacterial artificial chromosomes (BACs) and a chromosome-walking strategy on an index case of CCSK with t(10;17)(q22;p13) by karyotype, we identified the chromosomal breakpoints on 17p13.3 and 10q22.3. The translocation results in rearrangement of YWHAE on chromosome 17 and FAM22 on chromosome 10, producing an in-frame fusion transcript of ∼3 kb, incorporating exons 1-5 of YWHAE and exons 2-7 of FAM22, as determined by RT-PCR using YWHAE- and FAM22-specific primers. The YWHAE-FAM22 transcript was detected in six of 50 further CCSKs tested, therefore showing an overall incidence of 12% in our cohort. No transcript-positive cases presented with stage I disease, despite this being the stage for 31% of our cohort. Tumour cellularity was significantly higher in the cases that were transcript-positive. Based on the chromosome 10 breakpoint identified by FISH and the sequences of the full-length transcripts obtained, the FAM22 members involved in the translocation in these CCSK cases include FAM22B and FAM22E. Elucidation of the role of YWHAE-FAM22 in CCSK will assist development of more efficient and targeted therapies for this childhood cancer, which currently has poor outcomes.
authors.affiliation: National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
authors.forename: Elaine
authors.initials: E
authors.lastname: O'Meara
authors.forename: Deirdre
authors.initials: D
authors.lastname: Stack
authors.forename: Cheng-Han
authors.initials: CH
authors.lastname: Lee
authors.forename: A Julian
authors.initials: AJ
authors.lastname: Garvin
authors.forename: Thomas
authors.initials: T
authors.lastname: Morris
authors.forename: Pedram
authors.initials: P
authors.lastname: Argani
authors.forename: Jeong S
authors.initials: JS
authors.lastname: Han
authors.forename: Jenny
authors.initials: J
authors.lastname: Karlsson
authors.forename: David
authors.initials: D
authors.lastname: Gisselson
authors.forename: Ivo
authors.initials: I
authors.lastname: Leuschner
authors.forename: Manfred
authors.initials: M
authors.lastname: Gessler
authors.forename: Norbert
authors.initials: N
authors.lastname: Graf
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Fletcher
authors.forename: Maureen J
authors.initials: MJ
authors.lastname: O'Sullivan
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D056905:Chromosome Breakpoints; D016386:Chromosome Walking / Q000379:methods; D022202:Chromosomes, Artificial, Bacterial; D002879:Chromosomes, Human, Pair 10; D002886:Chromosomes, Human, Pair 17; D016172:DNA Fingerprinting; D005260:Female; D005453:Fluorescence; D005456:Fluorescent Dyes; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D011379:Prognosis; D018227:Sarcoma, Clear Cell / Q000235:genetics* / Q000556:secondary; D014178:Translocation, Genetic
chemical_list: D048948:14-3-3 Proteins; D005456:Fluorescent Dyes; C482983:YWHAE protein, human