Cell-free DNA - a promising biomarker
The detection and genetic analysis of circulating cell-free DNA (cfDNA) in plasma may provide a promising dynamic biomarker that can distinguish cancer patients from other patients with non-neoplastic disease.
The team at the Leicester ECMC led by Professor Jacqui Shaw is developing technology for the extraction and analysis of cell-free DNA from plasma as a marker for different mutations and disease burden in a number of different cancers. In this particular study the team investigate cfDNA as a biomarker to identify breast cancer patients who will relapse with metastatic disease.
The potentially long interval between resection of primary tumours and relapse suggests a period of dormancy, where there is growth restriction of unseen micrometastases. It is well established that treatment is more effective when given before overt metastatic disease develops, which highlights the need for sensitive markers of minimal disease. A number of classical factors (e.g., type, grade, node status, and hormone receptor status) and prognostic and predictive markers (e.g., HER2, Ki-67) are used to determine individual risk, but these are assessed in the primary tumour removed by surgery and are not useful in monitoring minimal disease. Moreover, genetic changes can occur between metastases and the primary tumour.
Copy number (CN) variations (CNVs) are amplified or deleted regions of the genome, of variable size, which are recognized as a major source of normal human genome variability and contribute significantly to phenotypic variation. In this particular study
CNVs found in cfDNA in patients’ plasma mirrored those found in the primary tumour indicating this is a promising marker to predict breast cancer patients who may relapse.
The team at the Leicester ECMC are now leading a UK-wide consensus on standards and priority areas for research in cfDNA across a number of cancers including an ECMC-funded review of all studies in this area to identify opportunities and gaps in knowledge and a sample sharing study to help standardise collection and analysis across centres.