Gaurav Sharma ’22

The epigenetic components pertaining to the onset of cancer have been of interest for many years due to the hope of developing approaches to delay the onset of cancer in the future for an individual. Recently, a tumor suppressor family has been discovered, called Ras-Association Domain Family (RASSF) which epigenetically inactivated breast, lung, skin, and thyroid cancers. Neither RASSF10’s in-vivo function nor its role in kidney cancer has been studied yet, but researchers from the Institute of Genetics in Germany suspect that it may also play a role in kidney cancer. 

In order to study the effects of inactivating/silencing RASSF10 in kidney cancer, these researchers developed the first RASSF10 knockout mouse model. The mice showed no physical difference from regular mice and were still fertile. Double knockouts (p53 and RASSF10 or RASSF1A and RASSF10) were used as well. Researchers noticed an increase in tumorigenesis and spleen enlargement in the double knockout mice. Specifically, the p53/RASSF10 double knockout showed neoplasia in the kidney. Survival of the RASSF10 knockout mice decreased while KRAS, a protein that signals proliferation or differentiation, and MYC, a collection of transcription factors for tumorigenesis, activity increased. Researchers then looked at cells from human kidney cancer and found that RASSF10 was inactivated in these cell lines as well. This observation supported the hypothesis that RASSF10 inactivation may also be a component responsible for kidney cancer in humans.  

These findings pose a possible target area in which researchers can develop an approach to activate RASSF10. One possible methodology suggested by the researchers is epigenetic editing similar to the method that created the knockout mice. Researchers also now have an approach to find other genes that may be inactivated and promote tumorigenesis. Hypermethylation was the primary sign of inactivation in RASSF10 so screening genes that are hypermethylated in knockouts may reveal more tumorigenesis candidate genes. The next step for researchers would be uncovering the details in the pathway of RASSF10 to see exactly how inactivating RASSF10 leads to kidney cancer.  

[1] A. Richter, et al., RASSF10 is frequently epigenetically inactivated in kidney cancer and its knockout promotes neoplasia in cancer prone mice.Oncogene (2020). https://doi.org/10.1038/s41388-020-1195-6

[2] Image retrieved from: https://www.nature.com/articles/s41388-020-1195-6#auth-6