Detection of Rare Mutations by Duplex DNA Sequencing

Focus: 

To further develop a method of double-stranded genomic DNA sequencing to capture specific cancer-associated genes, which promises 10,000-fold more accuracy than the best current technology

Anticipated Impact: 

A method that would be significantly better at early detection of cancer, monitoring patients for tumor recurrence, and optimizing selection of targeted and personalized therapy

Abstract: 

DNA sequencing is increasingly used in the diagnosis and treatment of human disease. Current error rates are as high as one in a thousand, which prevents accurate sequencing of rare mutations or identification of rare cells in a heterogeneous tumor. Proposed is the further development of a novel method of sequencing, duplex sequencing, which simultaneously sequences both strands of DNA. Other technologies sequence only one strand which makes it impossible to differentiate a reading error from a genuine mutation (a genuine mutation will be represented on both strands). Ultimately, this technology is expected to improve monitoring of tumor recurrence and optimize selection of drugs for personalized therapy, and, because it is applicable to any condition where DNA sequencing is valuable, the impact should be broad.

Cancer Diagnostics, Therapeutics

Grant Update

Principal Investigator:
Lawrence Loeb
Grantee Organization:
University of Washington
Grant Title:
Detection of Rare Mutations by Duplex DNA Sequencing
Grant Cohort and Year:
2013 Proof of Concept (03)
Grant Period:
05/01/2013 - 04/30/2014 (Completed)
Grant Amount:
$250,000
Progress on the grant supported by the Life Science Discovery Fund has been excellent. We have developed a new method for DNA sequencing that gives us unprecedented accuracy. Using this method we can identify rare mutations present in tumors prior to diagnosis. This would allow us to target these mutations and prevent them from being selected resulting in the emergence of resistance to chemotherapeutic agents.

Impact in Washington

Location of LSDF Grantee
Locations of Collaborations/Areas of Impact
Seattle

Legislative Districts:
11, 34, 36, 37, 43, 46

Health Impacts

Cancer Diagnostics, Therapeutics