Year: 2021
Type: article
Abstract: Quantitation of rare somatic mutations is essential for basic research and translational clinical applications including minimal residual disease (MRD) detection. Though unique molecular identifier (UMI) has suppressed errors for rare mutation detection, the sequencing depth requirement is high. Here, we present Quantitative Blocker Displacement Amplification (QBDA) which integrates sequence-selective variant enrichment into UMI quantitation for accurate quantitation of mutations below 0.01% VAF at only 23,000X depth. Using a panel of 20 genes recurrently altered in acute myeloid leukemia, we demonstrate quantitation of various mutations including single base substitutions and indels down to 0.001% VAF at a single locus with less than 4 million sequencing reads, allowing sensitive MRD detection in patients during complete remission. In a pan-cancer panel and a melanoma hotspot panel, we detect mutations down to 0.1% VAF using only 1 million reads. QBDA provides a convenient and versatile method for sensitive mutation quantitation using low-depth sequencing.
Source: Nature Communications
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,560
Awards: Lung Cancer Screening via Ultrasensitive and Cost-efficient Analysis of Tumor DNA Signatures in Blood, G4813539592, Highly multiplexed and mutation-sensitive quantitative PCR for cancer diagnostics, G7785730620, Prevalence of Rare Passenger Mutations in Biopsy Tissue as Cancer Stratification Markers
OpenAlex ID: W3171641674