An evaluation of the Agrobacterium tumefaciens Virulence gene system as a potential diagnostic test for Neuroblastoma.

Abstract

Neuroblastoma is a common pediatric cancer, the prognosis for which is markedly dependent upon the progression of the disease at the time of diagnosis. It has been argued that a mass screening programme for all infants would aid early detection of neuroblastoma and reduce mortality. Neuroblastoma is unusual amongst childhood cancers since the basis for such a test exsists - otherwise asymptomatic patients excrete abnormal amounts of specific phenolic compounds in their urine. The presence of these metabolites at elevated levels is taken as diagnostic of the disease. A number of pilot screening programmes in different parts of the world have shown that a quick, inexpensive and reliable method of screening is needed. One candidate for this is a test based upon the responses of Agrobacterium tumefaciens to compounds with structures similar to those produced as a result of tumour metabolism. This bacterium responds to such phenolic ligands chemotactically and by induction of virulence gene expression. Data presented in this work shows that phenolics secreted by neuroblastoma tumours are incapable of inducing virulence gene expression but are capable of acting as chemoattractants. The role of phosphorylation in VirA/G mediated phenolic chemotaxis is investigated. Evidence is presented that phosphorylation of Vir and G is required for chemotaxis. A novel, highly reproducible and comparible measure bacterial chemotaxis, the chemotactic index is derived and applied.