DNA damage may re-regulate cancer gene regulatory mechanisms

  Understanding the mechanisms that mediate extensive DNA damage in cancer genomes has always been the most interesting research area for cancer researchers. According to a recent study published in the international journal Genome Biology, which was recognized by scientists at Baylor College of Medicine and other institutions, changes in genome structure are changes in DNA methylation (gene regulation) in human cancers . It can be used as a special mechanism.

  In this article, the researchers collected whole-genome sequencing, gene expression and DNA methylation data of more than 1,400 human cancers. They found that structural changes constantly change DNA methylation, which affects the expression of hundreds of genes. This overall reduces the overall level of cancer DNA methylation. Researcher Chad Clayton (Chad Clayton) found that when DNA fragments are sequenced, there are two DNA fragments in the genome, because when certain DNA fragments in the genome are moved to different locations, the structure of the genome changes. Fusion occurred on the Internet and interfered with the genetic instructions encoded by DNA. The researchers analyzed the effects of changes in genome structure on DNA methylation and gene expression in human cancers. They analyzed the human cancer genome map and data from the genome-wide pancreatic cancer analysis project. These data include molecules in the entire genome. These changes include protein-coding genes and regulatory regions of various cancer cells, and the same information from non-cancerous tissues is used as a research control.

  Researchers have found that in many cancer types, changes in genome structure play a very important role in changes in DNA methylation. DNA methylation is a special method of controlling gene expression, and it is also the epigenome. The epigenome partially contains all chemical modifications to DNA, and is also directly related to proteins that regulate gene expression within the genome. Researcher Clayton said that in different types of cancer, changes in methylation usually occur in a non-random way. Some of these genes were previously known to be related to cancer, but researchers have identified some genes that were previously thought to be unrelated to cancer, and some genes may be directly involved in the cause of the patient.

  Generally, structural changes are associated with a decrease in the overall level of DNA methylation. In cancer, the epigenome changes. In current research, structural changes are an important mechanism for changing the epigenome. Researchers believe that in specific cancers, different cancers do not have the same number of structural mutations. Some cancers may not change much, but the structure of some cancers is widely distributed, so researchers can effectively classify cancers based on structural changes. Correlation analysis can also provide researchers with other information.

  For example, researchers found that cancers with high levels of DNA changes tend to have lower levels of immune cell invasion. This may be very important for the development of cancer immunotherapy. The results of this paper show that structural changes not only play an important role in annotating DNA sequence errors, but also affect DNA expression at the epigenetic level. Later, when researchers look for genetic causes of cancer, they may study the effects of structural changes on DNA.