文章：

早发性与平均发病年龄结直肠癌人群的基因组景观对比研究

Genomic Landscapes of Early-Onset Versus Average-Onset Colorectal Cancer Populations

原文发布日期：28 February 2025

DOI: 10.3390/cancers17050836

类型: Article

开放获取: 是

英文摘要：

Background: Rates of early-onset colorectal cancer (eoCRC), defined as disease diagnosed at <50 years of age, are increasing. The incidence and spectrum of somatic and pathogenic germline variants (PGV) in this population are not well understood. Methods: This cross-sectional study leveraged Tempus’ clinicogenomic database, including de-identified records of patients diagnosed with CRC between 2000–2022, to analyze and compare eoCRC and average-onset colorectal cancer (aoCRC, disease diagnosed ≥50 years of age) patients. The frequency and spectrum of somatic mutations and PGVs in patients with eoCRC and aoCRC were evaluated and compared. Results: Among 11,006 participants in this study, 57% were male, 76% were white, and 80% had stage 4 disease. Within the total cohort, 2379 had eoCRC and 8627 had aoCRC. Among patients with eoCRC, 4.2% had a tumor with high microsatellite instability and/or deficient mismatch repair (MSI-H/dMMR) and 6.8% with aoCRC had an MSI-H/dMMR tumor (p< 0.001). The most frequent somatic mutations involvedTP53,APC, andKRAS, with the most significant difference inBRAF, which was more frequently mutated in aoCRC (9.8% vs. 4.7%,p< 0.0001). In total, 1413 (59.4%) eoCRC and 4898 (56.8%) aoCRC patients had matched normal specimen (blood or saliva) sequencing and a PGV was identified in 6.9% of eoCRC and 5.0% of aoCRC patients. Conclusions: Somatic and germline mutation profiles were similar for eoCRC and aoCRC patients and may not adequately explain differences in tumor behavior and age of disease onset.

摘要翻译： 

背景：早发性结直肠癌（定义为诊断年龄<50岁）的发病率正在上升。该人群的体细胞和致病性胚系变异的发生率及谱系尚不明确。方法：本横断面研究利用Tempus临床基因组数据库（包含2000年至2022年间诊断为结直肠癌患者的去识别化记录），对早发性结直肠癌和平均发病年龄结直肠癌（诊断年龄≥50岁）患者进行分析比较。评估并比较了两组患者的体细胞突变和致病性胚系变异的频率及谱系特征。结果：在11,006名研究参与者中，57%为男性，76%为白人，80%处于疾病IV期。总体队列中，2379例为早发性结直肠癌，8627例为平均发病年龄结直肠癌。早发性结直肠癌患者中4.2%存在高度微卫星不稳定性和/或错配修复缺陷肿瘤，而平均发病年龄结直肠癌组该比例为6.8%（p<0.001）。最常见的体细胞突变涉及TP53、APC和KRAS基因，差异最显著的是BRAF基因突变——平均发病年龄结直肠癌组的突变频率显著更高（9.8% vs. 4.7%，p<0.0001）。共有1413例（59.4%）早发性结直肠癌和4898例（56.8%）平均发病年龄结直肠癌患者进行了匹配正常样本（血液或唾液）测序，其中早发性结直肠癌组6.9%、平均发病年龄结直肠癌组5.0%检测到致病性胚系变异。结论：早发性结直肠癌与平均发病年龄结直肠癌患者的体细胞和胚系突变谱相似，可能不足以充分解释肿瘤行为及发病年龄的差异。

原文链接：

Genomic Landscapes of Early-Onset Versus Average-Onset Colorectal Cancer Populations