Release date: 2017-04-17
Aneuploidy variation, the abnormal number of chromosomes in cells, is responsible for many types of cancers and genetic diseases, including Down's syndrome, and is the cause of most spontaneous abortions. It is unusual for the severity of the disease caused by aneuploidy variation to be significantly individualized. For example, nearly 90% of Down's syndrome fetuses will spontaneously abort. However, patients with Down syndrome can live to more than 60 years of age.
46 chromosomes of human cells (Source: NIH official website)
In the past, researchers believed that this difference was caused by differences in the genetic makeup of individual patients. But recently, in an article published in the journal Cell, researchers at the Massachusetts Institute of Technology (MIT) found that aneuploidy mutations cause significant differences in traits in cells with identical genetic information.
This finding may have a major impact on cancer treatment because it can explain why cancer cells carrying the same genetic information respond differently to the same therapy.
Immediate effect of aneuploidy variation
Aneuploidy occurs because chromosomes cannot be properly separated during cell division or are not evenly distributed between two daughter cells. Humans normally have 46 chromosomes, and in the case of aneuploidy, the number of chromosomes in the cell will be too much or too little.
Professor Angelika Amon of the Massachusetts Institute of Technology led the study to study the effects of aneuploidy variation on phenotypes by inducing chromosomes to increase or lose in yeasts with the same genetic information. The reason for choosing yeast is that it is very similar to human cells. The results show that the induced changes in the number of chromosomes directly affect the phenotype of the cell.
Professor Amon said: "After inducing chromosomal variation, we found that the responses between different cells are very different. Some cells completely slow down the replication cycle and no longer continue to divide; while other cells divide normally, only slightly affected. ."
Corresponding author Angelika Amon (Source: MIT official website)
The study also systematically analyzed the effects of increasing or losing different chromosomes on cells. The researchers found that even if different cells increase or lose the same chromosome, these cells behave very differently.
Not only affect cell division
In addition to cell division, the study also validated the effects of aneuploidy variation on other biological pathways, including transcription and response to environmental changes. Transcription is the process by which DNA information is transferred to RNA and is the first step in gene expression. The results show that the same cells containing aneuploidy variation are very different in terms of transcription and response to environmental changes. This suggests that aneuploidy variation has an important impact on many biological processes.
To ensure that the conclusions of the study were not related to yeast cells, the researchers performed the same experiment in mice and found that aneuploidy variants caused similar trait differences.
The study found that aneuploidy itself can lead to trait variability, providing another explanation for the variability of disease caused by aneuploidy. In addition, it also makes sense for cancer treatment. Tumors are composed of different cell populations, and the genetic variation between tumor cells is quite large. Gene mutations are often thought to be the leading cause of failure in chemotherapy or other therapies because one treatment may not be able to target all cells within the tumor.
Effect of aneuploidy variation on cells (Source: Cell)
Professor Giulia Rancati of the Institute of Biomedical Research at the Singapore Institute of Science and Technology (A*STAR) believes that understanding the effects of aneuploidy variation on cell phenotype is a fundamental biological problem for the treatment of various diseases such as cancer and Down. Syndrome is of great significance.
Professor Rancati commented: "This exciting new work has deepened our understanding of how aneuploidy variability causes phenotypic variation, revealing that cells carrying the same aneuploid karyotype will have unexpectedly high cells. Inter-heterogeneity. We know that cancer cell evolution is associated with multiple drug resistance, so it is an interesting topic to study whether aneuploidy has an impact on the evolution of cancer cells."
Next, Professor Amon hopes to further study the origin of aneuploidy variation. “We are working hard to find key genes and critical pathways. Once we find the critical path, we can develop new cancer treatments,†she said.
Source: WuXi PharmaTech
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