In a new study published in the July 3 issue of Cell, a team of scientists from the Salk Institute of Biology found that micronucleus destruction can cause a large amount of DNA damage on the chromosome, possibly in the process of cancer formation China has played a more active role than previously thought. They also found that for many solid tumors, including non-small cell lung cancer (NSCLC), micronucleus destruction can serve as a common objective biomarker for their genetically unstable state.

Professor Martin Hetzer of the Laboratory of Molecular and Cell Biology of the Salk Institute of Biology said: "Our research shows that in solid tumors such as NSCLC, more than 60% of micronuclei have catastrophic dysfunction. We are in two major Micronucleus destruction was found in the subtype of human non-small cell lung cancer, which indicates that it can be used as a valuable cancer diagnostic tool. "

Due to the wrong operation of cell division, sometimes the chromosome will appear outside the nucleus. During normal cell division, the cell copies its chromosomes, and then divides them evenly into two newly formed daughter cells, each of which has a set of chromosomes. However, for various reasons, sometimes the chromosomes are not evenly distributed, resulting in an extra chromosome being received in one daughter cell, while the other daughter cell is short of chromosomes. These lagging chromosomes usually don't go to the nucleus, but end up wrapped in their own nuclear membrane elsewhere in the cell. Micronuclei appear in cancer cells at a higher frequency.

In their research, Hetzer and the research team found that there was a previously unknown defect in the nuclear fibrous layer at a certain stage of cancer cell division, causing devastating damage to the nuclear membrane surrounding the micronucleus, causing it to lose its basic nucleus Functions such as replication, transcription, DNA damage recognition and repair, etc. After nuclear membrane destruction, more than 60% of micronuclei developed irreversible dysfunction, which promoted the formation of carcinogenic aneuploidy.

Hemier laboratory assistant researcher Emily Hatch said: "In the micronucleus, we see the formation of holes in the nuclear fibrous layer. I think that at these hole sites, the nuclear membrane loses its support, which weakens and breaks. We have not fully understood The reason for this phenomenon in the micronucleus. "

Previous studies have confirmed that nuclear membrane damage can cause DNA damage and gene transcriptional arrest, and promote the formation of aneuploidy. The damaged DNA then enters the next generation of daughter cells, undergoing a chromothripsis process, resulting in a large amount of DNA damage and tumor formation.

In the current study, Hatch found identifiable

Biomarkers of micronucleus destruction, which may greatly improve the ability of pathologists to identify these structures in tumor sections. At present, the diagnosis of several cancers depends on the identification of aneuploidy, and there are only a few objective markers that can be used to detect the instability of the solid tumor genome.

Hetzer said: "We provide a new method for assessing aneuploidy in these tissues: identification of micronucleus destruction in solid tumors." Although it is unclear how many cancers are affected by micronucleus destruction. In addition to NSCLC, scientists believe that micronucleus destruction may also play a role in bone cancer, melanoma, and other types of lung cancer.

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