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中国医学科学院肿瘤医院吴晨等研究人员合作揭示食管癌癌前病变到癌变发展过程中的基因组变化。该项研究成果于2023年11月30日在线发表在《癌细胞》杂志上。

研究人员表示，食管鳞状细胞癌（ESCC）是通过一系列日益异常的癌前病变发展而来的。以往的研究揭示了正常食管上皮细胞与ESCC之间在拷贝数改变（CNA）和基因突变方面的显著差异，这些改变和突变推动了克隆的扩张。然而，由于早期癌前病变的数据有限，这些转变的时间以及其中哪些是恶性转化的先决条件仍不清楚。

研究人员分析了来自正常食管、早期和晚期癌前病变以及食管癌的1275份微活检样本，以解读每个阶段的基因组改变。研究表明，TP53双链失活的频率在早期癌前病变阶段急剧增加，而在晚期阶段，CNA和APOBEC诱变则大幅增加。TP53双拷贝缺失是细胞周期、DNA修复和细胞凋亡通路中的基因发生CNA的先决条件，这表明它可能是启动恶性转化的最早步骤之一。

附：英文原文

Title: Genomic alterations driving precancerous to cancerous lesions in esophageal cancer development

Author: Jiang Chang, Xuan Zhao, Yichen Wang, Tianyuan Liu, Ce Zhong, Yueqiong Lao, Shaosen Zhang, Han Liao, Fan Bai, Dongxin Lin, Chen Wu

Issue&Volume: 2023-11-30

Abstract: Esophageal squamous cell carcinoma (ESCC) develops through a series of increasinglyabnormal precancerous lesions. Previous studies have revealed the striking differencesbetween normal esophageal epithelium and ESCC in copy number alterations (CNAs) andmutations in genes driving clonal expansion. However, due to limited data on earlyprecancerous lesions, the timing of these transitions and which among them are prerequisitesfor malignant transformation remained unclear. Here, we analyze 1,275 micro-biopsiesfrom normal esophagus, early and late precancerous lesions, and esophageal cancersto decipher the genomic alterations at each stage. We show that the frequency of TP53 biallelic inactivation increases dramatically in early precancerous lesion stagewhile CNAs and APOBEC mutagenesis substantially increase at late stages. TP53 biallelic loss is the prerequisite for the development of CNAs of genes in cell cycle,DNA repair, and apoptosis pathways, suggesting it might be one of the earliest stepsinitiating malignant transformation.

DOI: 10.1016/j.ccell.2023.11.003

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00394-X

Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：38.585
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