Ultra-sensitive Genetic Mutation Detection by 4D Sequencing

Project: Research

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Detecting cancer-associated genetic alterations in circulation is emerging as a promising approach to detect cancer, to assess treatment response and to monitor drug resistance in a non-invasive manner. It has been demonstrated that circulating tumor DNA (ctDNA) can be detected in ~50% of patients with early stage/localized tumors across 14 tumor types. Numerous methods have been developed, to our knowledge, none has been able to robustly detect ultra-low fraction mutations (e.g. <0.01%) and at the same time achieve a good number of targets (hundreds) efficiently, including BEAMing, TAm-Seq, multiplex COLD-PCR, microdroplet-based methods (e.g. Raindance ThunderBolts) and AMP-seq. The high error rate associated with PCR and next generation sequencing can be reduced by methods such as Safe-Seq and Duplex Sequencing. The duplex sequencing has been used for targeted sequencing, however, the requirement of high sample inputs limits its broad applications where ctDNA amounts are often limited. Promising biomarkers such as mutations in tumor suppressor genesTP53andSMAD4have been shown to occur in a stage-specific manner in esophageal adenocarcinoma and in pancreatic cancer. We aim to develop methods that could meet the requirements of ultra-sensitive/specific, broad coverage, and high-efficiency to fully realize the potential of ctDNA sequencing.


Project number9667135
Grant typeARG
Effective start/end date1/05/1610/12/18