EPIGENETICINACTIVATION OF RASSF1A IN MALIGNANT CUTANEOUS MELANOMAS

ABSTRACT
RAS is a superfamily of genes that encode for a group of small GTPases. These are involved in various signal transductions. The active form of the proteins eventually interact with another group of proteins which are knows as RAS effector proteins. RASSF1A (RAS association domain family 1A) is gene that encodes one of the RAS effector proteins. This is a tumor suppressor gene. It is associated with cell cycle control, microtubule stabilization, cellular adhesion, motility and apoptosis (Peters, 2007). In another study (Shivkumar,2002), they found that RASSF1A regulates cyclinD1 which is a cell cycle regulator. A mutation in this gene is related to a large number of tumors. In this article, we discuss the inactivation of the RASSF1A gene due to hypermethylation at 2 promoter regions. The study detected that 55% of the tumors show hypermethylation, while all the normal skin sample showed no methylation. Methylation is detected by Methylation Specific PCR(MSP). The RASSF1A gene having hypermethylation in both regions showed no gene expression. The basis for the epigenetic mutation of RASSF1A still remains unclear. But the presence of hypermethylation only in tumor cells indicates the roles of RASSF1A either in the initiation or the progression of the tumors. It has been established that the frequency of hypermethylation of RASSF1A in melanoma tumors is greater than 25%. The discovery of the of the role of RASSF1A in tumors can cause a break through in the developments of anti-cancer drugs.

By

Crystal D'Souza