Prevalence of Molecular Alterations in a Swiss Cohort of 512 Colorectal Carcinoma Patients by Targeted Next-Generation Sequencing Analysis in Routine Diagnostics

Abstract

<b><i>Introduction:</i></b> Colorectal carcinoma (CRC) is among the most common carcinomas in women and men. In the advanced stage, patients are treated based on the <i>RAS</i> status. Recent studies indicate that in the future, in addition to <i>KRAS</i> and <i>NRAS</i>, alterations in other genes, such as <i>PIK3CA</i> or <i>TP53</i>, will be considered for therapy. Therefore, it is important to know the mutational landscape of routinely diagnosed CRC. <b><i>Method:</i></b> We report the molecular profile of 512 Swiss CRC patients analyzed by targeted next-generation sequencing as part of routine diagnostics at our institute. <b><i>Results:</i></b> Pathogenic and likely pathogenic variants were found in 462 (90%) CRC patients. Variants were detected in <i>TP53</i> (54.3%), <i>KRAS</i> (48.2%), <i>PIK3CA</i> (15.6%), <i>BRAF</i> (13.5%), <i>SMAD4</i> (10.5%), <i>FBXW7</i> (7.8%), <i>NRAS</i> (3.5%), <i>PTEN</i> (2.7%), <i>ERBB2</i> (1.6%), <i>AKT1</i> (1.5%), and <i>CTNNB1</i> (0.9%). The remaining pathogenic alterations were found in the genes <i>ATM</i>(<i>n</i>= 1), <i>MAP2K1</i>(<i>n</i>= 1), and <i>IDH2</i>(<i>n</i>= 1). <b><i>Discussion/Conclusions:</i></b> Our analysis revealed the prevalence of potential predictive markers in a large cohort of CRC patients obtained during routine diagnostic analysis. Furthermore, our study is the first of this size to uncover the molecular landscape of CRC in Switzerland.