Longitudinal monitoring of tumour burden with a modified Guthrie card

The ability to sequence DNA from a Guthrie card e.g. genomic or methylomic analysis (also see my post from last Summer) makes their more routine use in cancer genomics studies attractive. An area that would be great to see developed is the extraction of the cell-free DNA from a blood spot. This would be incredibly easy for patients to use and potentially allow very long term studies to be performed without visits to a clinic for a blood draw.

There are some big hurdles to overcome. A blood spot does not contain a lot of blood so the amount of cell-free DNA is likely to be very low restricting analysis to variants at high allele frequency. Also cell free DNA is likely to be contaminated with high-molecular weight genomic DNA, further diluting cell-free alleles. But for some applications this is not a problem.

Ideally cell-free DNA would be eluted/analysed separately from the genomic DNA from PBMCs for downstream mutation analysis. Current extraction methods lyse cells to extract maximum yield, but this lysis could possibly be avoided for ctDNA methods? The company Circulogene, spun out of Johns Hopkins in, is developing nucleic acid extraction products based on its proprietary Nanobind technology. Most recently their new pan-cancer NGS panel test was covered on GenomeWeb where Chen-Hsiung Yeh (CSO) described the 3,000 hotspot, 50 gene panel, which uses their ctDNA isolation technology. Technological improvements that allowed the use of dried blood spots may not be "on the cards" (sorry for the pun) for Circulogene, but I do hope someone is working on similar ideas.

Blood spot cards could be easily mailed out to patients and posted back to a central lab for processing. Adding information via 2D barcodes would allow fully automated test analysis so patients could be matched up to specific NGS panel tests.