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.

中文翻译：

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年轻与老年大肠癌无细胞循环 DNA 谱的新基因组差异

我们提出了第一个分析，检查利用临床可用的无细胞循环肿瘤 DNA (cfDNA) 检测在一组诊断为 <50 岁与 50 岁以上的晚期结直肠癌 (aCRC) 患者中检测到的分子改变。使用来自 5873 名患者的 cfDNA 测试比较了患者特征和突变频率。<50 岁的患者在APC、CTNNB1和SMAD4 中有更多的序列改变，以及更高频率的局灶性BRAF和ERBB2 (HER2) 扩增。我们的研究增加了进一步的证据，表明年轻和年老发病的 CRC 可能具有不同的分子基础，具有预后和治疗意义。