| First Author | Richter AM | Year | 2020 |
| Journal | Oncogene | Volume | 39 |
| Issue | 15 | Pages | 3114-3127 |
| PubMed ID | 32047266 | Mgi Jnum | J:299543 |
| Mgi Id | MGI:6490749 | Doi | 10.1038/s41388-020-1195-6 |
| Citation | Richter AM, et al. (2020) RASSF10 is frequently epigenetically inactivated in kidney cancer and its knockout promotes neoplasia in cancer prone mice. Oncogene 39(15):3114-3127 |
| abstractText | Kidney cancer incidences are rising globally, thereby fueling the demand for targeted therapies and precision medicine. In our previous work, we have identified and characterized the Ras-Association Domain Family encoding ten members that are often aberrantly expressed in human cancers. In this study, we created and analyzed the Rassf10 knockout mice. Here we show that Rassf10 haploinsufficiency promotes neoplasia formation in two established mouse cancer models (Rassf1A(-/-) and p53(-/-)). Haploinsufficient Rassf10 knockout mice were significantly prone to various diseases including lymphoma (Rassf1A(-/-) background) and thymoma (p53(-/-) background). Especially Rassf10(-/-) and p53-deficient mice exhibited threefold increased rates of kidney cysts compared with p53(-/-) controls. Moreover, we observed that in human kidney cancer, RASSF10 is frequently epigenetically inactivated by its CpG island promoter hypermethylation. Primary tumors of renal clear cell and papillary cell carcinoma confirmed that RASSF10 methylation is associated with decreased expression in comparison to normal kidney tissue. In independent data sets, we could validate that RASSF10 inactivation clinically correlated with decreased survival and with progressed disease state of kidney cancer patients and polycystic kidney size. Functionally, we revealed that the loss of Rassf10 was significantly associated with upregulation of KRAS signaling and MYC expression. In summary, we could show that Rassf10 functions as a haploinsufficient tumor suppressor. In combination with other markers, RASSF10 silencing can serve as diagnostic and prognostic cancer biomarker in kidney diseases. |
