Abstract
The incidence of colorectal cancer (CRC) in younger patients is rising, mostly due to tumors in the descending colon and rectum. Therefore, we aimed to explore the molecular differences of left-sided CRC between younger (≤45 years) and older patients (≥65). In total, 1,126 CRC tumor samples from the splenic flexure to (and including) the rectum were examined by next-generation sequencing (NGS), immunohistochemistry, and in situ hybridization. Microsatellite instability (MSI) and tumor mutational burden (TMB) were assessed by NGS. Younger patients (n = 350), when compared with older patients (n = 776), showed higher mutation rates in genes associated with cancer-predisposing syndromes (e.g., Lynch syndrome), such as MSH6 (4.8% vs. 1.2%, p = .005), MSH2 (2.7% vs. 0.0%, p = .004), POLE (1.6% vs. 0.0%, p = .008), NF1 (5.9% vs. 0.5%, p < .001), SMAD4 (14.3% vs. 8.3%, p = .024), and BRCA2 (3.7% vs. 0.5%, p = .002). Genes involved in histone modification were also significantly more mutated: KDM5C (1.9% vs. 0%, p = .036), KMT2A (1.1% vs. 0%, p = .033), KMT2C (1.6% vs. 0%, p = .031), KMT2D (3.8% vs. 0.7%, p = .005), and SETD2 (3.2% vs. 0.9%, p = .039). Finally, TMB-high (9.7% vs. 2.8%, p < .001) and MSI-high (MSI-H; 8.1% vs. 1.9%, p = ...Continue Reading
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