Genomic landscape of cell-free DNA in patients with colorectal cancer [Research Briefs]

"Liquid biopsy" approaches analyzing cell-free DNA (cfDNA) from the blood of cancer patients are increasingly utilized in clinical practice. However, it is not yet known whether cfDNA sequencing from large cancer patient cohorts can detect genomic alterations at frequencies similar to those observed by direct tumor sequencing, and whether this approach can generate novel insights. Here, we report next-generation sequencing data from cfDNA of 1,397 colorectal cancer (CRC) patients. Overall, frequencies of genomic alterations detected in cfDNA were comparable to those observed in three independent tissue-based CRC sequencing compendia. Our analysis also identified a novel cluster of extracellular domain (ECD) mutations in EGFR, mediating resistance by blocking binding of anti-EGFR antibodies. Patients with EGFR ECD mutations displayed striking tumor heterogeneity, with 91% harboring multiple distinct resistance alterations (range 1-13, median 4). These results suggest that cfDNA profiling can effectively define the genomic landscape of cancer and yield important biologic insights.

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