PCR-based amplification of circulating RNAs as prognostic and predictive biomarkers – Focus on neuroblastoma

Metastatic disease is a major challenge for cancer cure, haematogenous spread and subsequent growth of tumour cells at distant sites being the cause of most cancer deaths. Molecular characterization and detection of the tumour cells responsible for haematogenous spread may increase understanding of the biology of metastasis, help improve patient management and allow evaluation of novel treatments to prevent and eradicate this disease. The bone marrow is a common site to which tumour cells metastasize, from which they may re-circulate to other organs with a favourable microenvironment for growth. The detection of tumour cells in blood suggests one route for metastasis, and provides an accessible, minimally invasive liquid sample through which it may be possible to monitor and detect minimal disease and early signs of metastasis. Significant improvements in the sensitivity and specificity of tumour cell detection have been made, such that it is now possible to unambiguously detect a single tumour cell in over 10 million normal cells. However, the clinical impact of such low level disease and how to interpret the natural variation that can arise from sequential sampling of bone marrow aspirates and blood is currently largely unknown. This commentary will focus on the technical advancements and application of reverse transcriptase polymerase chain reaction to detect cancer mRNAs in bone marrow and blood, and discuss the potential clinical impact of this test in neuroblastoma.