http://www.nature.com/news/cancer-biomarkers-written-in-blood-1.15624
DNA circulating in the bloodstream could guide cancer treatment — if researchers can work out how best to use it.
But researchers have found ways to get a richer view of a patient's cancer, and even track it over time. When cancer cells rupture and die, they release their contents, including circulating tumour DNA (ctDNA): genome fragments that float freely through the bloodstream. Debris from normal cells is normally mopped up and destroyed by 'cleaning cells' such as macrophages, but tumours are so large and their cells multiply so quickly that the cleaners cannot cope completely.
The first practical use of circulating DNA came in another field. Dennis Lo, a chemical pathologist now at the Chinese University of Hong Kong, reasoned that if tumours could flood the blood with DNA, surely fetuses could, too. In 1997, he successfully showed that pregnant women carrying male babies had fetal Y chromosomes in their blood6. That discovery allowed doctors to check a baby's sex early in gestation without disturbing the fetus, and ultimately to screen for developmental disorders such as Down's syndrome without resorting to invasive testing. It has revolutionized the field of prenatal diagnostics (see Nature 507, 19; 2014).
Despite its promise, ctDNA is not yet ready for a starring role in the clinic. For one thing, the most sensitive techniques for detecting it, such as BEAMing, rely on some knowledge of which mutations to look for. This knowledge can be provided by taking a biopsy, sequencing its mutations, designing patient-specific molecular probes that target them, and using those probes to analyse later blood samples — a laborious approach that must be repeated for each patient. The alternative is to use exome sequencing, as Rosenfeld's team did. This requires no previous knowledge about the cancer, but it is prohibitively expensive to sequence and analyse every sample at the depth required to detect rare mutant fragments.
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