Novel Genomic Differences in Cell-Free Circulating DNA Profiles of Young- Versus Older-Onset Colorectal Cancer

Abstract

We present the first analysis examining molecular alterations detected utilizing a clinically available cell-free circulating tumor DNA (cfDNA) assay in a cohort of patients with advanced colorectal cancer (aCRC) diagnosed <50 versus ≥50 years of age. Patient characteristics and mutation frequencies were compared using cfDNA tests from 5873 patients. Patients <50 had more sequence alterations in APC, CTNNB1, and SMAD4, as well as a higher frequency of focal BRAF and ERBB2(HER2) amplifications. Our study adds further evidence suggesting that young- versus older-onset CRC may have distinct molecular underpinnings, with prognostic and therapeutic implications.

Keywords: cell-free DNA; liquid biopsy; precision medicine; young-onset CRC.