| Accession |
PRJCA015964 |
| Title |
Biallelic inactivation of TP53 and elevated copy-number alterations promote clonal expansion at early stage of esophageal carcinogenesis |
| Relevance |
Medical |
| Data types |
Whole genome sequencing
Exome
|
| Organisms |
Homo sapiens
|
| Description |
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. |
| Sample scope |
Monoisolate |
| Release date |
2024-08-09 |
| Publication |
| PubMed ID |
Article title |
Journal name |
DOI |
Year |
| 38039962
|
Genomic alterations driving precancerous to cancerous lesions in esophageal cancer development
|
Cancer Cell
|
10.1016/j.ccell.2023.11.003
|
2023
|
|
|
| Grants |
| Agency |
program |
Grant ID |
Grant title |
| 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
|
|
|
|
| Submitter |
Chen
Wu (chenwu@cicams.ac.cn)
|
| Organization |
Cancer Hospital, Chinese Academy of Medical Sciences |
| Submission date |
2023-03-31 |
