Objective There are few studies which characterised the molecular alterations in premalignant colorectal adenomas. Our major goal was to establish colorectal adenoma genome atlas and identify molecular markers of progression from colorectal adenoma to adenocarcinoma. Design Whole-exome sequencing and targeted sequencing were carried out in 149 adenoma samples and paired blood from patients with conventional adenoma or sessile serrated adenoma to characterise the somatic mutation landscape for premalignant colorectal lesions. The identified somatic mutations were compared with those in colorectal cancer (CRC) samples from The Cancer Genome Atlas. A supervised random forest model was employed to identify gene panels differentiating adenoma from CRC. Results Similar somatic mutation frequencies, but distinctive driver mutations, were observed in sessile serrated adenomas and conventional adenomas. The final model included 20 genes and was able to separate the somatic mutation profile of colorectal adenoma and adenocarcinoma with an area under the curve of 0.941. Conclusion The findings of this project hold potential to better identify patients with adenoma who may be candidates for targeted surveillance programmes and preventive interventions to reduce the incidence of CRC.

中文翻译：

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癌前结直肠腺瘤的体细胞突变图谱

目的描述癌前结直肠腺瘤分子改变的研究较少。我们的主要目标是建立结直肠腺瘤基因组图谱并确定从结直肠腺瘤进展到腺癌的分子标记。设计 在 149 个腺瘤样本和来自常规腺瘤或无柄锯齿状腺瘤患者的配对血液中进行了全外显子组测序和靶向测序，以表征癌前结直肠病变的体细胞突变情况。将鉴定的体细胞突变与来自癌症基因组图谱的结直肠癌 (CRC) 样本中的突变进行比较。采用有监督的随机森林模型来识别区分腺瘤与 CRC 的基因组。结果 相似的体细胞突变频率，但不同的驱动突变，在无柄锯齿状腺瘤和常规腺瘤中观察到。最终模型包括 20 个基因，能够以 0.941 的曲线下面积将结直肠腺瘤和腺癌的体细胞突变谱分开。结论 该项目的发现有可能更好地识别腺瘤患者，这些患者可能是有针对性的监测计划和预防干预措施的候选人，以降低 CRC 的发病率。