A Comparative Genomic Analysis of Left- and Right-Sided Colon Cancer Using Real-World Data from the AACR Project GENIE BPC Dataset

Right-sided colon cancer (RCC) and left-sided colon cancer (LCC) exhibit distinct clinical and molecular characteristics, influencing prognosis and therapeutic strategies. This study analyzed 750 patients with histologically confirmed adenocarcinoma (RCC: 387, LCC: 363) from the AACR Project Genomics Evidence Neoplasia Information Exchange (GENIE) Biopharma Collaborative (BPC) dataset. Tumor mutation burden (TMB) was significantly higher in RCC (6.65 ± 11.3) than in LCC (3.17 ± 4.35, adjusted p = 3.12 × 10 ^-32 ). After filtering for functionally significant mutations, RCC exhibited enrichment for BRAF (23.1% vs. 6.7%, adjusted p = 1.64 × 10 ^-8 ), KMT2D (8.6% vs. 3.2%, adjusted p = 9.27 × 10 ^-3 ), and SMAD4 (13.1% vs. 7.3%, adjusted p = 2.97 × 10 ^-2 ) mutations, while LCC demonstrated a higher frequency of TP53 (40.6% vs. 31.8%, adjusted p = 2.97 × 10 ^-2 ). Multivariate Cox regression analysis showed significantly poorer overall survival (OS) in RCC than in LCC (HR: 1.30, 95% CI: 1.02–1.66, p = 0.033). KRAS mutations were identified as an independent predictor of worse OS in RCC (HR: 1.68, 95% CI: 1.06–2.70, p = 0.027), while BRAF mutations were associated with poorer OS in LCC (HR: 1.58, 95% CI: 1.05–2.37, p = 0.028).