I have blogged about the liquid biopsy for about eight years (see, for example, Rapid Adoption of the Term "Liquid Biopsy" on the Web; Continuing Discussion about the "Liquid Biopsy"; "Liquid Biopsy" Used to Refer to Detection of Any Serum Cancer DNA). Initially, the test involved the isolation of circulating cancer cells from a blood sample, a daunting task due to their rarity, and the subsequent analysis of the DNA of them. Liquid biopsy research has evolved since then to the collection and analysis of cell-free circulating DNA and RNA. A recent article discussed how Grail, the apparent leader in the commercialization of the technology, has selected what it deems to be the best method for cancer detection in the blood (see: Grail, the liquid biopsy startup, picks an approach for its cancer test). Below is an excerpt from the article:
Grail, the company that has raised $1.6 billion to develop a blood test to detect cancer early, announced Monday that it has settled on a method for its test and enrolled 115,000 patients in two large clinical trials. A third study, with 50,000 patients, has already begun. The San Francisco-based startup, spun out of DNA sequencing giant Illumina in 2016, previously presented data on three different approaches to detect cancer using DNA circulating in the blood. One used DNA sequencing to look at specific regions of genes; a second used the technology to sequence the entire genomes of cells floating in patients’ bloodstreams; and a third looked at methylation, an epigenetic change across the whole genome. Grail said in a statement that it has settled on the third method, which uses methylation to detect cancer and identify where in the body it started.....The company also said that it had received a special “breakthrough device” designation from the Food and Drug Administration that could expedite the test’s eventual review.
Here's a paragraph from the Grail landing page about how to analyze cancer signals in blood:
An increasing body of evidence suggests tumors release cell-free nucleic acids (cfNAs) into the bloodstream. cfNAs are small fragments of DNA and RNA, and reflect the genomic features of the tumor from which they originated. cfNAs are thought to be a direct measure of cancer and can be detectable in the bloodstream of people with cancer, potentially even before symptoms present.
All of this seems promising. Grail certainly has generous funding and is enrolling large numbers of patients in its clinical trials. However, I suspect that, even with its “breakthrough device” classification by the FDA, we won't have good answers about this technology for several years. Here's a brief description of the science of DNA methylation patterns (see: DNA Methylation and Its Basic Function):
In the mammalian genome, DNA methylation is an epigenetic mechanism involving the transfer of a methyl group onto the C5 position of the cytosine to form 5-methylcytosine. DNA methylation regulates gene expression by recruiting proteins involved in gene repression or by inhibiting the binding of transcription factor(s) to DNA. During development, the pattern of DNA methylation in the genome changes as a result of a dynamic process involving both de novo DNA methylation and demethylation. As a consequence, differentiated cells develop a stable and unique DNA methylation pattern that regulates tissue-specific gene transcription.
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