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Esophageal Squamous Cancer from 4NQO-Induced Mice Model: CNV Alterations.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2022 Nov 18; Vol. 23 (22). Date of Electronic Publication: 2022 Nov 18. - Publication Year :
- 2022
-
Abstract
- Squamous esophageal carcinoma is a common pathological type of esophageal carcinoma around the world. The prognosis of esophageal carcinoma is usually poor and diagnosed at late stages. Recently, research suggested that genomic instability occurred in esophageal cells during the development of esophageal squamous cell carcinoma (ESCC). Identifying prognostic and specific genomic characteristics, especially at the early hyperplasia stage, is critical. Mice were given 4-nitroquinoline 1-oxide (4NQO) with drinking water to induce esophageal cancer. The immortalized human esophageal epithelial cell line (NE2) was also treated with 4NQO. We performed histologic analyses, immunofluorescence, and immunohistochemical staining to detect DNA damage at different time points. Whole-exome sequencing was accomplished on the esophagus tissues at different pathological stages to detect single-nucleotide variants and copy number variation (CNV) in the genome. Our findings indicate that all mice were tumor-forming, and a series of changes from simple hyperplasia (ESSH) to intraepithelial neoplasia (IEN) to esophageal squamous cell carcinoma (ESCC) was seen at different times. The expression of γ-H2AX increased from ESSH to ESCC. In addition, mutations of the Muc4 gene were detected throughout the pathological stages. Furthermore, CNV burden appeared in the esophageal tissues from the beginning of ESSH and accumulated more in cancer with the deepening of the lesions. This study demonstrates that mutations caused by the early appearance of DNA damage may appear in the early stage of malignant tissue before the emergence of atypia. The detection of CNV and mutations of the Muc4 gene may be used as an ultra-early screening indicator for esophageal cancer.
- Subjects :
- Humans
Mice
Animals
DNA Copy Number Variations
Hyperplasia
Esophageal Squamous Cell Carcinoma chemically induced
Esophageal Squamous Cell Carcinoma genetics
Esophageal Neoplasms chemically induced
Esophageal Neoplasms genetics
Esophageal Neoplasms pathology
Carcinoma, Squamous Cell chemically induced
Carcinoma, Squamous Cell genetics
Carcinoma, Squamous Cell pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 23
- Issue :
- 22
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 36430789
- Full Text :
- https://doi.org/10.3390/ijms232214304