A molecular genetic investigation of rhabdomyosarcoma

Chalk, Jeremy (1998). A molecular genetic investigation of rhabdomyosarcoma. PhD thesis The Open University.

DOI: https://doi.org/10.21954/ou.ro.0000e13a

Abstract

Alveolar Rhabdomyosarcoma IS characterised by a t(2;13)(q35;qI4) chromosome trartslocation, which leads to the fusion of the P AX3 artd the FKHR genes. The resulting fusion gene encodes a chimeric protein which has aberrant transcriptional activity. The data here describes the molecular definition of the genomic breakpoints on both derivative chromosomes in one case and the derivative chromosome 13 breakpoints in two other cases. The DNA sequences adjacent to the breakpoints on the derivative chromosome 13 are remarkable for their resemblartce to recognition sequences for the protein trartslin. Electrophoretic mobility shift studies (EMSA) confirm that these sequences bind translin. These findings suggest that translin may not only be important in the genesis of chromosomal trartslocations in lymphoid malignancy, but also in translocations found in solid tumours.

Mutation analysis of tumour samples and cell lines from patients with embryonal and alveolar rhabdomyosarcoma suggests that there are no subtle disease associated mutations within the P AX3 gene that could contribute towards the neoplastic state.