High-Depth Sequencing of Over 750 Genes Supports Linear Progression of Primary Tumors and Metastases in the Majority of Patients with Liver-Limited Metastatic Colorectal Cancer

摘要

Background: Colorectal cancer with metastases limited to the liver (liver-limited mCRC) is a distinct clinical subset characterized by possible cure with surgery. We performed high-depth sequencing of over 750 cancer-associated genes and Nanostring copy number profiling in matched tissue (primary/metastasis/normal) to characterize genomic progression in 18 patients with liver-limited mCRC. Results: High depth (a median of 385-fold base coverage) Illumina sequencing and use of 3 variant callers (GATK-based, MuTect and LoFreq) enabled comprehensive and accurate identification of somatic variants down to 2.5% variant allele frequency (95% true positive and 97% true negative validation rate by Ion Torrent). We identified a median of 11 somatic single nucleotide variants (SNVs) per tumor.