RASSF1A and its epigenetic dysregulation in genitourinary cancer: a current update

RASSF1A is a tumor suppressor and is underexpressed in most cancers including genitourinary malignancies. RASSF1A is most frequently inactivated epigenetically following biallelic hypermethylation of its CpG islands involving DNA methyltransferases. Genitourinary malignancies result in profound morbidity and mortality especially in the old age people and hence discovery of novel therapeutic agents targeting the molecular aberrations are demanded for improved survival. In bladder cancer, RASSF1A downregulation is associated with modulation of key signaling process such as Hippo signaling pathway. Also, pharmacological activation of RASSF1A could augment the cytotoxicity induced by chemotherapeutic agents. Promoter methylation in RASSF1A in combination with other tumor suppressor genes (such as GSTP1 and MGMT) is also observed in the cancers of the male reproductive system and may aid in pathological classification as well as differentiation. In prostate cancer, RASSF1A promoter hypermethylation status could have key role in early diagnosis or modulating therapeutic response. Genitourinary malignancies having RASSF1A hypermethylation are also linked to poor patient prognosis. Evaluating RASSF1A methylation in a panel consisting of other tumor suppressor genes could plausibly improve the diagnostic accuracy in genitourinary cancers. Also, novel hypomethylating agents targeting the RASSF1A promoters could potentially enhance its reactivation in genitourinary cancers.