Comparison of plasma ctDNA from the portal and peripheral veins of resectable CRC patient



Abstract:

Background: Circulating tumor DNA (ctDNA) holds great potential as a biomarker for cancer management. Unfortunately, with a half-life of < 2hrs, ctDNA is present in miniscule quantities and can go undetected in peripheral blood. We hypothesized that blood collected from the portal vein may yield higher quantities of ctDNA than that collected elsewhere for colorectal cancers (CRC) due to the passage of blood from gastrointestinal organs through the portal vein prior to circulation. Methods: 10mL of peripheral blood was collected from 12 CRC patients prior to or during tumor removal surgery during which an additional 10 mL of blood drawn from the portal vein. ctDNA fragment length and concentration was measured for every pair of the resulting ctDNA, along with tissue gDNA, was sequenced using Accu-Act, a NGS panel of 61 genes which have implication of cancer treatments. Concordance of ctDNA mutation profiles from both collection sites and tumor were compared. Results: ctDNA was detected in all 12 sample pairs and a comparison of ctDNA from both collection sites revealed similar fragment lengths and concentration (12.26ng/ml, and peripheral vein: 10.83ng/ml). Little difference in concordance (compared to tumor) was observe. Though the average minor allele frequency of somatic mutations from portal venous ctDNA was slightly higher than that of peripheral venous ctDNA, the difference is not substantial. A mumber of mutaions with low allele frequcy (down to 0.1%, 2 copies), were detected in both sites, and from two independent DNA extractions from each sites. Conclusions: We have demonstrated the feasibility of obtaining portal venous ctDNA and reported no substantial difference between portal venous and peripheral venous ctDNA. Even the sensitivity and reporducbility of our Nebula-Firefly are very high, this analysis is still susceptible to sampling errors associated with the low copy number of mutated ctDNA in circulation and larger studies may provide more conclusive results.


Website: http://abstract.asco.org/176/AbstView_176_170474.html



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