Extended Data Table 2 Cross-platform validation using a generic approach to ctDNA profiling
From: Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution
- a, 7 out of 10 (70%) of bespoke-panel ctDNA-positive patients had tumour SNVs detectable in plasma preoperatively by a generic hotspot PCR NGS lung panel (Lung Oncomine, Thermofisher). The three bespoke-panel ctDNA-positive patients undetected by the generic panel had mean clonal plasma VAFs lower than the 0.1% plasma VAF limit of detection reported for the generic panel (shaded yellow). b, On the basis of the CT volumetric assessment of each patient’s primary tumour we predicted plasma VAF corresponding to a tumour of that size (see Fig. 3 and Methods for details of the approach). This allowed us to infer platform sensitivities for each patient within the bespoke-panel non-detected cohort. Six LUADs (shaded green; CRUK0037, CRUK0051, CRUK0004, CRUK0039, CRUK0025 and CRUK0048) had tumour volumes approximating to a plasma VAF of more than 0.1%. This suggested that these tumours resided within the top platform sensitivity bracket of both the generic and bespoke-panel ctDNA platforms. No ctDNA was detected by either platform in these cases, suggesting biological specificity of the bespoke-panel. c, Hotspot SNVs not identified in tumour tissue through exome sequencing were identified in plasma of 9 out of 28 patients by the generic panel. This suggested a non-tumour origin of cfDNA, platform non-specificity or an evolving minor subclone or second primary. DOR, depth of read; ND, not detected. Combined exome VAF (unfiltered), VAF across all tumour regions analysed (without call filters).
