| Summary: | Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood, and comprises a group of heterogeneous malignancies accounting for approximately 10% of all solid tumours in children under 15 years of age. It is a member of the small round blue cell tumours (SRBCT) family. Two main subtypes of RMS are recognised: embryonal (ERMS) and alveolar (ARMS). As is the case for many members of the SRBCT group, ARMS is characterised in 80% of cases by a specific chromosomal rearrangement [t(2;13)(q35;q14) or t(1;13)(p36;q14)] that gives rise to a fusion gene <i>[PAX3/FOXO1A </i>or<i> PAX7/FOXO1A]</i>. The fusion genes are believed to function as aberrant transcription factors. Characterisation of aberrant fusion proteins in human cancer has provided novel diagnostic and prognostic tools, and in some cases novel therapeutic strategies. To date no known cytogenetic abnormality characteristic of ERMS has been identified. This thesis reports the molecular cytogenetic investigation of nine ERMS cell lines (RD, 7763, CT10, RH36, YM, HX170, CCA, JR1, RUCH2) in an attempt to identify a consistent chromosomal aberration for ERMS, the most prevalent RMS subtype. Composite karyotypes of four cell lines (CCA, JR1, RUCH2 and RUCH3) were constructed following the application of an in house molecular cytogenetic screening protocol. A panel of nine ERMS cell line karyotypes was subsequently analysed from which chromosome 15 was revealed to be one of the most frequently rearranged chromosomes in ERMS. Detailed physical mapping of all breakpoints containing chromosome 15 in these nine cell lines suggested a number of genes potentially disrupted; but did not identify a consistent chromosomal aberration. A number of reciprocal chromosomal translocations were identified in the nine ERMS cell lines, and these were investigated in detail. A t(2;15)(q36;q11) in HX170 was noted to result in the disruption of <i>PAX3</i>, and may lead to the formation of a novel fusion gene in this cell line.
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