Rassf2, short for Ras association domain family member 2, is a tumor suppressor gene [1,2,3,4,6,7]. It contains Ras association and SARAH domains and binds directly to K-Ras in a GTP-dependent manner via the Ras effector domain [6]. Rassf2 is involved in multiple biological processes such as apoptosis, cell cycle arrest, and regulation of Rac GTPase signaling [2,5,6]. It is also associated with pathways like the Hippo pathway through interaction with Hippo kinases MST1 and MST2 [2,5].

Rassf2 methylation is significantly higher in gastric cancer tissues compared to adjacent non-tumor tissues, indicating its potential in predicting the risk of gastric cancer, though not for tumor metastasis [1]. In Ewing sarcoma, Rassf2 methylation is frequent, correlating with poor overall survival, especially in patients under 18 years old [3]. In squamous cervical cancer, Rassf2 hypermethylation is related to lower expression, vascular invasion, and shorter survival [4]. In breast cancer, Rassf2 hypermethylation patterns differ between luminal and non-luminal subtypes, and it is associated with better prognosis in multivariate analysis [7].

In conclusion, Rassf2 functions as a tumor suppressor involved in apoptosis, cell cycle regulation, and GTPase signaling. Its methylation status is closely associated with the prognosis of several cancers including gastric, Ewing sarcoma, squamous cervical, and breast cancer. Understanding Rassf2 through in-vivo studies could potentially provide new insights into cancer development and treatment.