For cancer earlier detection, researchers are seeking to develop methodologies that are less invasive than current diagnostic tests, which would allow them to be performed on more people and at a higher frequency. Liquid biopsies, taking advantage of cancer-specific biomarkers such as tumour-derived DNA in the blood, urine or saliva, are an attractive opportunity for a minimally invasive diagnostic assay.
Methylation and hydroxymethylation of cytosine (5mC and 5hmC) are chemical epigenetic modifications of DNA that are associated with changes in gene expression. Levels of 5mC and 5hmC are altered in cancer and so detection of methylation on circulating tumour DNA within blood samples could form the basis of a blood-based cancer test. However, up until now, the main method for detecting these modifications relied on harsh bisulphite treatment, making it challenging to measure levels in samples with low amounts of DNA such as liquid biopsies. In this paper published in Nature Biotechnology, OxCODE researchers from Chunxiao Song’s and Benjamin Schuster-Böckler’s groups at the Ludwig Institute for Cancer Research develop TAPS (TET-assisted pyridine borane sequencing), a novel bisulphite-free, base resolution and highly sensitive method for measuring 5mC and 5hmC, in addition to detecting DNA mutations and copy number variations.
Research in Chunxiao Song's and Benjamin Schuster-Böckler's labs is funded by: