| 项目编号 |
PRJCA015964 |
| 项目标题 |
Biallelic inactivation of TP53 and elevated copy-number alterations promote clonal expansion at early stage of esophageal carcinogenesis |
| 涉及领域 |
Medical |
| 数据类型 |
Whole genome sequencing
Exome
|
| 物种名称 |
Homo sapiens
|
| 描述信息 |
Esophageal squamous cell carcinoma (ESCC) develops through a series of increasingly abnormal precancer- ous lesions. Previous studies have revealed the striking differences between normal esophageal epithelium and ESCC in copy number alterations (CNAs) and mutations in genes driving clonal expansion. However, due to limited data on early precancerous lesions, the timing of these transitions and which among them are pre-requisites for malignant transformation remained unclear. Here, we analyze 1,275 micro-biopsies from normal esophagus, early and late precancerous lesions, and esophageal cancers to decipher the genomic alterations at each stage. We show that the frequency of TP53 biallelic inactivation increases dramatically in early precancerous lesion stage while 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 steps initiating malignant transformation. |
| 样品范围 |
Monoisolate |
| 发布日期 |
2024-08-09 |
| 出版信息 |
| PubMed ID |
文章标题 |
杂志名称 |
Doi |
发表年份 |
| 38039962
|
Genomic alterations driving precancerous to cancerous lesions in esophageal cancer development
|
Cancer Cell
|
10.1016/j.ccell.2023.11.003
|
2023
|
|
|
A Circulating GPNMB-Based Multimodal Model Integrates Tumor-Immune Crosstalk to Predict Immunotherapy Response in Esophageal Cancer
|
Cancer Discovery
|
10.1158/2159-8290.CD-25-1907
|
2025
|
| 41799568
|
Ectopic CD11c Drives SMAD3-Mediated Aberrant Antigen Presentation and Epithelial–Mesenchymal Transition in Esophageal Squamous Cell Carcinoma
|
Cancer Communications
|
10.34133/cancomm.0014
|
2026
|
|
|
| 项目资金来源 |
| 机构 |
项目类型 |
授权项目ID |
授权项目名称 |
| National Natural Science Foundation of China (NSFC)
|
|
81988101
|
|
| Ministry of Science and Technology of the People's Republic of China (MOST)
|
National Key Technologies R&D Program
|
2021YFC2502000
|
|
| Chinese Academy of Medical Sciences
|
Medical and Health Technology Innovation Project of Chinese Academy of Medical Sciences
|
2021-I2M-1-013
|
|
| Chinese Academy of Medical Sciences
|
Medical and Health Technology Innovation Project of Chinese Academy of Medical Sciences
|
2022-I2M-2-003
|
|
|
|
| 提交者 |
Chen
Wu (chenwu@cicams.ac.cn)
|
| 提交单位 |
Cancer Hospital, Chinese Academy of Medical Sciences |
| 提交日期 |
2023-03-31 |
