Breakthrough in renal cancer research in children

With the development of embryo, cells have to learn how to deal with thousands of genes they carry This is why every cell has a detailed gene expression manual, which lists in detail which genes should be activated, to what extent and when Photo source: Laboratory of chromium biology and genetics at the Rockefeller University In order to fulfill the contents of their respective operation manuals, cells will use chromatin reading protein to identify which genes need to be expressed Recently, in a research report published in the international journal Nature, scientists from Rockefeller University discovered a problem in the process of gene regulation, which may promote the malignant transformation of normal cells and generate Wilms tumor (Wilms' tumor, one of the most common renal cancers in children), the findings may help develop new therapies The results of this study also raise questions about other types of cancer The researchers found that the related reading proteins may be able to cause problems by acquiring a new characteristic and becoming active Researcher Liling Wan said: 'we have not observed this mechanism before Now we ask whether this type of molecular mechanism has also been hijacked by other types of cancer? Many years ago, researchers found that the reading protein called enl can participate in the pathogenesis of childhood leukemia by activating the oncogene Now researchers turn to the study of Wilms tumor They found that some patients with Wilms tumor also carry mutations in the gene encoding enl In order to see whether these mutations are indeed involved in the pathogenesis of Wilms' tumor, Wan and his colleagues introduced the mutation into mouse embryonic stem cells, and then induced cells to develop into kidneys in a culture dish To the researchers' surprise, after inserting the mutation, they were able to observe that a tumor like structure would appear in the developing kidneys , which is similar to the human Wilms tumor we usually see Then the researchers deeply understood how the enl mutation transformed cells into tumor cells In the cells carrying the mutation and unchanged, the position of the enl protein in the genome is the same, which shows that the mutant enl protein can effectively identify which genes will be expressed However, the accumulated mutant protein in these sites will cause genes to be continuously transcribed into RNA (this is gene inversion The first step to protein The abnormal gene expression can make cells feel confused They don't know what they will change into Instead of differentiating into mature kidney cells, cells will start to speed up proliferation and fall into an immature stage, which eventually leads to tumor formation, said Wan, the researcher Now that researchers have elucidated a previously unknown mechanism for this cancer, they want to know if it can return cancer cells to normal, such as the ability to use drugs to interfere with the binding of enl to the genome and form aggregates So far, researchers have evidence that intervention in any process may stabilize gene expression and allow cells to develop normally Original sources: Wan, L., Chong, S., Xuan, F et al Impressed cell fat through gain of function mutations in a chromium reader Nature 577, 121 – 126 (2020) doi: 10.1038/s41586-019-1842-7