Recent studies show that aneuploidy and driver gene mutations precede cancer diagnosis by many years^1,2,3,4. We assess whether these genomic signals can be used for early detection and pre-emptive cancer treatment using the neoplastic precursor lesion Barrett’s esophagus as an exemplar⁵. Shallow whole-genome sequencing of 777 biopsies, sampled from 88 patients in Barrett’s esophagus surveillance over a period of up to 15 years, shows that genomic signals can distinguish progressive from stable disease even 10 years before histopathological transformation. These findings are validated on two independent cohorts of 76 and 248 patients. These methods are low-cost and applicable to standard clinical biopsy samples. Compared with current management guidelines based on histopathology and clinical presentation, genomic classification enables earlier treatment for high-risk patients as well as reduction of unnecessary treatment and monitoring for patients who are unlikely to develop cancer.

最近的研究表明，非整倍性和驱动基因突变比癌症诊断早了很多年^1,2,3,4。我们评估这些基因组信号是否可用于早期检测和先发制人的癌症治疗，使用肿瘤前体病变 Barrett 食管作为示例⁵. 对 Barrett 食管监测中长达 15 年的 88 名患者进行的 777 份活检样本的浅全基因组测序表明，即使在组织病理学转化前 10 年，基因组信号也可以区分进展性疾病和稳定疾病。这些发现在 76 名和 248 名患者的两个独立队列中得到验证。这些方法成本低，适用于标准临床活检样本。与当前基于组织病理学和临床表现的管理指南相比，基因组分类可以对高危患者进行早期治疗，并减少不必要的治疗，并对不太可能患癌症的患者进行监测。