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| |  Gene Mutation Linked to Growth, Spread of Rhabdomyosarcoma BETHESDA, Md -- October 9, 2009 -- Researchers have identified a gene that may play a role in the growth and spread of rhabdomyosarcoma (RMS). The finding, published online October 5 in the Journal of Clinical Investigation, has revealed a potential new target for the treatment of this disease. Although progress has been made in increasing the overall survival of patients treated for RMS, less than 30% of children whose cancer has metastasised, survive more than 5 years. The newly implicated gene produces a substance called fibroblast growth factor receptor 4, also referred to as FGFR4 protein -- a protein belonging to the receptor tyrosine kinases family. Earlier research by this team and others had shown that the FGFR4 gene is highly expressed in RMS tumours. The gene is also expressed during muscle development but not in mature muscle cells. Although this finding suggested a role for FGFR4 protein in RMS, the way in which it might contribute to the disease was not known. In the new study, researchers from the National Cancer Institute (NCI) and the National Heart, Lung and Blood Institute (NHLB), Bethesda, Maryland, and colleagues at The Children’s Hospital in Westmead, Australia, and the Nationwide Children’s Hospital, Columbus, Ohio, first examined FGFR4 gene expression in RMS tumours from 94 patients for whom clinical follow-up data was available. They found that more than 7% of the tumours had mutations causing alterations in the tyrosine kinase portion of the FGFR4 protein. Four different mutations, 2 in each of 2 locations in the FGFR4 gene, were predicted to change the function of the FGFR4 protein. “Our study shows that, when FGFR4 is overactive, either due to increased expression or mutations, it plays a key role in the growth and spread of RMS and that this gene could be an important target for therapy,” said senior author Javed Khan, MD, National Cancer Institute’s Center for Cancer Research, Bethesda, Maryland. “It also emphasises that high-risk or metastatic cancers may harbour other critical, as yet undiscovered, mutations. Therefore, we and others are applying advanced next-generation techniques to sequence the entire genome to search for every mutation that may contribute to paediatric and other cancers, and thus discover potential targets for personalized or individualised treatment.”
SOURCE: National Institutes of Health
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