Developing High-Accuracy Sequencing Methods for Use in Early Cancer Detection, Disease Stratification, and Chemotherapy Resistance With Cell-Free DNA
Abstract
Recent efforts to understand the mutational landscape of tumors has resulted in a detailed cataloguing of diagnostic, prognostic, and clinically actionable mutations. Previous studies have identified a number of "driver" mutations, thought to be responsible for tumor formation, present in a significant proportion of non-small cell lung cancer patients. Detection of these mutations can help in early cancer detection, guide treatment options, or alert to the emergence of chemotherapy resistance, all of which could be harnessed to significantly improve survival. The advent of next-generation sequencing technology (NGS) has opened up the possibility of clinically exploiting ctDNA. Unfortunately, ctDNA from cancer comprises only a small fraction of all the overall amount of cell-free DNA in the blood stream. This issue, in conjunction with the high error rates of NGS technology, has proven to be a major impediment in developing minimally invasive tests to look for rare tumor specific mutations in the sea of normal cell-free DNA. In this grant, we developed a targeted gene panel for use with ultra-high accuracy Duplex Sequencing to detect therapy resistance in non-small cell lung cancer (NSCLC). We enrolled 40 NSCLC patients with a known clinically actional tumor mutation (BRAF, KRAS, EGFR, ALK, ERBB2, or ALK) and collected cell-free DNA (cfDNA) every 3 months for at least 1 year. We demonstrate the ability of Duplex Sequencing to sequence cfDNA with high efficiency (greater than 30 percent) and high accuracy to detect a tumor therapy resistance mutations.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2021
- Accession Number
- AD1165146
Entities
People
- Scott R. Kennedy
Organizations
- University of Washington