title: Molecular cytogenetic analysis consistently identifies translocations involving chromosomes 1, 2 and 15 in five embryonal rhabdomyosarcoma cell lines and a PAX-FOXO1A fusion gene negative alveolar rhabdomyosarcoma cell line.
abstract: Rhabdomyosarcoma in children is a "small round blue cell tumour" that displays skeletal muscle differentiation. Two main histological variants are recognised, alveolar (ARMS) and embryonal (ERMS) rhabdomyosarcoma. Whereas consistent chromosome translocations characteristic of ARMS have been reported, no such cytogenetic abnormality has yet been described in ERMS. We have used multiple colour chromosome painting to obtain composite karyotypes for five ERMS cell lines and one PAX-FOXO1A fusion gene negative ARMS. The cell lines were assessed by spectral karyotyping (SKY), tailored multi-fluorophore fluorescence in situ hybridisation (M-FISH) using series of seven colour paint sets generated to examine specific abnormalities, and comparative genomic hybridisation (CGH). This approach enabled us to obtain karyotypes of the cell lines in greater detail than previously possible. Several recurring cytogenetic abnormalities were demonstrated, including translocations involving chromosomes 1 and 15 and chromosomes 2 and 15, in 4/6 and 2/6 cell lines respectively. All six cell lines demonstrated abnormalities of chromosome 15. Translocations between chromosomes 1 and 15 have previously been recorded in two primary cases of ERMS by conventional cytogenetics. Analysis of the translocation breakpoints may suggest mechanisms of ERMS tumourigenesis and may enable the development of novel approaches to the clinical management of this tumour.
authors.affiliation: Hutchison/MRC Research Centre, Cambridge, UK. ir210@cam.ac.uk
authors.forename: I
authors.initials: I
authors.lastname: Roberts
authors.forename: A
authors.initials: A
authors.lastname: Gordon
authors.forename: R
authors.initials: R
authors.lastname: Wang
authors.forename: K
authors.initials: K
authors.lastname: Pritchard-Jones
authors.forename: J
authors.initials: J
authors.lastname: Shipley
authors.forename: N
authors.initials: N
authors.lastname: Coleman
mesh_terms: D002648:Child; D002877:Chromosomes, Human; D002878:Chromosomes, Human, Pair 1; D002884:Chromosomes, Human, Pair 15; D002889:Chromosomes, Human, Pair 2; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D018628:Gene Dosage; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007621:Karyotyping; D015514:Oncogene Proteins, Fusion; D000072041:PAX3 Transcription Factor; D051763:PAX7 Transcription Factor; D051761:Paired Box Transcription Factors; D018232:Rhabdomyosarcoma, Alveolar / Q000235:genetics*; D018233:Rhabdomyosarcoma, Embryonal / Q000235:genetics*; D012983:Soft Tissue Neoplasms / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D014178:Translocation, Genetic / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D004268:DNA-Binding Proteins; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; D015514:Oncogene Proteins, Fusion; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051763:PAX7 Transcription Factor; D051761:Paired Box Transcription Factors; D014157:Transcription Factors; C068686:Pax3 protein, mouse