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Methylation and hydroxymethylation of cytosine (5mC and 5hmC) are chemical epigenetic modifications of DNA that are associated with changes in gene expression. 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. In this paper published in Nature Biotechnology, Ludwig Oxford researchers from Chunxiao Song’s and Benjamin Schuster-Böckler’s groups 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. Since levels of 5mC and 5hmC change in cancer, detection of methylation on circulating tumour DNA within blood samples could form the basis of a blood-based cancer test. For more information, see the Ludwig Cancer Research press release and the Nature Biotechnology "Behind the Paper" blog.

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The Kriaucionis, Schuster-Boeckler and Tomkova groups show that DNA polymerase ε makes errors when replicating methylated CpGs, producing C>T mutations at CpG dinucleotides.