Chromosomal Instability and Epigenetic Alterations are two indicators for identifying cancer cell metastasis. One from Memorial Sloan. Albert Agustinus, a graduate student at Memorial Sloan Kettering Cancer Center (MSK), discovered that the micronucleus (MCN) produced by chromosomal instability will accumulate considerable epigenetic changes in the process of cell division, making Cancer has become more difficult to treat. This study was not only published in the well-known scientific journal Nature, but also opened up a new and potential research direction for basic science, which can also be applied to clinical care.
Chromosomal instability: a driving force behind genetic variation
Chromosomal instability refers to abnormal changes in the structure or number of chromosomes in a cell. Normally, a cell’s chromosomes should maintain a stable structure and number to maintain normal cell function and gene expression. However, chromosomal instability can lead to chromosomal deletions, rearrangements, or gains, which can negatively affect the genetic function of cells. For example, normal human cells usually contain 46 chromosomes, while cancer cells may have more than normal. Chromosomal instability allows cancer cells to create more genetic combinations as they divide, potentially allowing daughter cells to develop new resistances to escape immune cells or drugs.
Chromosomal instability can be inherited or acquired. Inherited chromosomal instability is often associated with mutations or defects in specific genes, which affect the proper maintenance of chromosome structure by cells. Acquired chromosomal instability can result from the influence of external factors, such as radiation, chemicals, or environmental stress, that can damage chromosome structure or affect chromosome repair mechanisms.
Epigenetics: the mystery of gene regulation
Epigenetics (Epigenetics) is to cause changes in genetic gene expression or cell phenotype (Phenotype) through certain mechanisms without changing the DNA sequence. Epigenetic information in cells includes different chemical modifications on DNA, RNA, or histones, such as methylation, acetylation, phosphorylation, and ubiquitination , these changes in genetic information will directly affect the cells. On the one hand, the study of epigenetics is very important for understanding the development, adaptation, and pathogenesis of diseases in organisms. On the other hand, it also provides a new perspective to explain the interaction between genes and the environment, and can provide a deeper understanding of individual differences. and the origin of genetic diversity.
Epigenetic changes turn genes in a cell on or off without modifying the cell’s DNA code. At present, studies have pointed out that the epigenetic changes of cancer cells are mainly due to the methylation of the promoter (Promotor), resulting in the non-expression of key tumor suppressor genes (Tumor suppressor genes, TSGs), or the excessive modification of oncogene DNA proteins, Increased expression of oncogenes, which eventually lead to cancer.
The Hidden Threat of Chromosomal Instability
Micronuclei are abnormal structures that develop during chromosomal instability during interphase, usually as a result of radiation or chemical agents affecting dividing cells. Micronuclei in cells are very rare and are normally cleared by cells automatically. When many micronuclei accumulate in a cell, it is a sign of a serious problem with the cell, which is often the case in cancer cells.
Studies have pointed out that chromosomes (Chromosome) are sealed in micronuclei, which will disturb the chromatin (Chromatin) structure that makes up chromosomes, and micronuclei are repeatedly formed and reincorporated into the main nucleus. After multiple cell division cycles, considerable expression will be accumulated. epigenetic changes. These changes lead to progressively widening differences between individual cancer cells within the same tumor. The greater the differences between individual cancer cells, the more likely it is to develop cells that are resistant to any treatment, allowing the cancer cells to persist and grow.
Exploring new ways of metastasis and treatment of cancer cells
In one experiment, the researchers placed a model chromosome into a micronucleus, which then reintegrated into the main nucleus. They compared the foreign chromosomes with those in situ, and Dr. Yael David found: “The model chromosome showed clear epigenetic and DNA changes, indicating that the entry of chromosomes into the micronucleus has an important effect on the epigenetic changes in the major nucleus, which It has an important impact on the metastasis and evolution of cancer cells.” The doctor also added that this experiment has opened up a new field of research on cancer. The research team of Harvard University and Dana-Farber Cancer Institute (Dana-Farber Cancer Institute) published the research results in the journal Nature at the same time and found that in addition to micronuclei, there are also chromosome bridges (Chromosome bridge) will affect cell chromosome stability, which supports the findings of the MSK team.
In addition to uncovering subtle changes inside cancer cells, the research also offers new hope for patients. Epigenetic changes are a reversible form of gene regulation, and several classes of related drugs have been developed. Chromosomal instability and the presence of micronuclei could serve as biomarkers that could help identify patients who are more likely to benefit from epigenetic-modifying drugs, said lead researcher Samuel Bakhoum, MD. In addition, these new findings are also expected to inspire research on other emerging cancer therapies. In the long run, another potential research direction is to explore how to prevent micronucleus rupture.
According to Dr. David, the relationship between the two cancer indicators is a new discovery of basic scientific research, and the next five years will provide many interesting explorations and potential clinical changes. Chromosomal instability and epigenetic changes are the reasons for the variability of cancer cells, making cancer more difficult to cure. However, the discovery of the relationship between these two phenomena also means that there will be better treatments for various cancers and cancer cell metastasis.
Further reading: Machine learning to classify autism spectrum disorder will help open precision treatment target research
References:
1. https://www.mskcc.org/news/msk-led-research-finds-unexpected-link-between-chromosomal-instability-and-epigenetic-alterations
2. https://www.nature.com/articles/s41586-023-06084-7
3. https://www.nature.com/articles/s41586-023-06157-7
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2023-07-05 06:55:46
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