Cancer Genetics and Epigenetics, 2025, Vol.13, No.2, 62-76 http://medscipublisher.com/index.php/cge 64 TP53 variations. The CDKN2Agene can produce two tumor-inhibiting proteins, called p16^INK4a and p14^ARF. After this gene is lost, the normal growth and division process of cells is disrupted, and cancer is more likely to form (Liu et al., 2017). In precancerous lesion (IEN) and EAC tissues, loss of the CDKN2A gene is often found, indicating that it plays a role in the early stage of cancer development (Liu et al., 2017). The loss of the CDKN2A gene, coupled with other genetic changes, makes the molecular characteristics of EAC very complex and may also affect the recovery of patients and their response to treatment (Hoppe et al., 2021). 3.1.3 Increase in the ERBB2 gene In some EAC patients, the number of ERBB2 (HER2) genes increases (amplidates), which is associated with rapid tumor growth and poor patient recovery. ERBB2 is a kind of signal protein. When its quantity is excessive, it will activate some signal channels within the cells, enabling the cells to continuously grow and survive. Drugs like trastuzumab, which specifically target ERBB2, have shown good therapeutic effects on EAC patients with ERBB2 gene alterations. This indicates that identifying these genetic changes is of great significance for formulating individualized treatment plans (Hoppe et al., 2021). 3.2 Epigenetic changes and their impacts 3.2.1 DNA methylation pattern DNA methylation is an important way of "acquired alteration" of genes and plays a significant role in regulating the activity of EACgenes. In EAC tissues, abnormal DNA methylation was found. In some places, the degree of methylation was too high, while in others it was too low (Jammula et al., 2017; Peng et al., 2017). If the methylation degree in the initiation region of a gene is too high, it will cause the genes that inhibit tumors to "not function", while if the overall methylation degree is too low, it will make the gene unstable and also activate oncogenes. Research analysis reveals that the changes in DNA methylation are closely related to alterations in gene activity. Based on these changes, EAC can be classified into different types, and the therapeutic effects for patients of different types are also different (Jammula et al., 2017; Peng et al., 2017). 3.2.2 Histone modification Histone undergoes changes such as acetylation and methylation, which is another type of "acquired changes" that can affect the structure and function of the EAC gene. These changes can control the "working state" of genes, making them start or stop working. The specific effect depends on which histone has changed. For instance, histone acetylation usually puts genes into "working mode", while the effect of histone methylation is somewhat different and should be judged based on the actual situation. Recent studies have shown that Rnas such as lncrna and mirna, which are not involved in protein synthesis, can affect the changes of histones and promote the formation of the "acquired genetic state" of EAC (Xiao et al., 2019). Understanding the complex connection between the mutations of the genes themselves and these "acquired changes" is crucial for the development of new treatment methods targeting the "acquired state" of the EACgene (Peng et al., 2017). 4 Chromosomal Alterations and Copy Number Changes 4.1 Main chromosomal issues of EAC Esophageal adenocarcinoma (EAC) shows obvious chromosomal instability, which plays a key role in the formation of the disease. An important finding in the development from Barrett's esophagus (BE) to EAC is the existence of multiple rounds of chromosomal instability. This instability is often caused by errors in cell division and is exacerbated as the tumor suppressor gene TP53 loses its function. Abnormal cell division processes, including the replication of the entire genome, can cause changes in the number of chromosome copies, and the changes in chromosome fragments are driven by the continuous breaking-fusion-bridging cycle and unstable breaks of bicromeric chromosomes (Stachler et al., 2023). Research has found that when the content of purine-free/pyrimidine-free endonuclease 1 (APE1) increases, it disrupts the normal DNA recombination process and cell division cycle, making the genes of EAC unstable and thereby promoting tumor growth. In cancer cells, if the inhibition of APE1 takes effect, the cells will stop dividing and growth will also be affected, which indicates that it is very important for maintaining chromosome stability (Kumar et al., 2023). In addition, in the tissues of patients who developed from Barrett's esophagus (BE) to severe
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