Sci TransL Med: An analytical method to improve the sensitivity of ctDNA sequencing!

The dna (ctDNA) of the source of circulating tumors can be used to monitor cancer dynamics without invasivenessCtDNA testing can be challenging for patients with small volumes of small plasma or small fragments of DNA originating from tumors or residual lesionsWan et alhave found that by analyzing hundreds to thousands of mutations first identified by tumor genotypes, the sensitivity of plasma ct DNA testing can be increasedIn, the researchers outlined the integration of the VAriant Reads (INVAR) pipeline, which combines a custom error suppression method and signal enrichment method based on the biological characteristics of ctDNAIn this way, the test limits in each sample can be independently estimated based on the number of informational readings sequenced across the gene base of multiple specific patientsresearchers applied INVAR to customized mixed-capture sequencing data from 176 plasma samples from 105 patients with early and latemelanoma, lung cancer, kidney cancer, glioma serotonin, andbreast cancerBy integrating signals with a median reading greater than 105 readings, the ctDNA is routinely quantified to one mutation per 100,000 molecules, and in some cases (e.gwith a higher tumor mutation load and/or plasma mixture) to a few millionthsthe method results in a curve-down area (AUC) value of 0.98, while the early and challenging ctDNA detection setting is 0.80The researchers extended this approach to full exoon sequencing and genome-wide sequencing, and found that as long as tumor mutation lists were available, INVAR could be applied without the need for personalized sequencingas tumor sequencing increases, this method for personalized cancer monitoring can increase the sensitivity of cancer fluid biopsies