Epigenetically inactivated RASSF1A as a tumor biomarker

Abstract

RASSF1A represents one of the eight isoforms of the RASSF1 gene. RASSF1A is a tumor suppressor gene whose inactivation influences tumor initiation and development. In cancer, RASSF1A is frequently inactivated by mutations, loss of heterozygosity and, most commonly, by promoter hypermethylation. As epigenetic inactivation of RASSF1A was detected in various cancer types, it was extensively investigated and nowadays, the research on RASSF1A promoter methylation proceeds in the light of an epigenetic tumor biomarker. Analyses of DNA methylation of genes involved in carcinogenesis such as RASSF1A are currently done mostly on genomic DNA (gDNA). Simultaneously, cell-free DNA (cfDNA) from liquid biopsies has lately been developed as an early cancer diagnostic tool. This review discusses the evidence on aberrantly methylated RASSF1A in gDNA and cfDNA from different cancer types and its utility for early cancer diagnosis, prognosis, and surveillance. Furthermore, methylation frequencies of RASSF1A in gDNA and cfDNA were compared in various cancer types. The weaknesses and strengths of the investigations mentioned above are discussed. In conclusion, although the importance of RASSSF1A methylation in relation to cancer was established, and it became included in several diagnostic panels, the evidence of its diagnostic utility is still experimental and not yet implemented in standard clinical health care.

Salivary DNA Methylation as an Epigenetic Biomarker for Head and Neck Cancer. Part II: A Cancer Risk Meta-Analysis

“…The RASSF1A gene prevents tumorigenesis through multiple cellular process, such as cell cycle arrest, migration, microtubular stabilization, and apoptosis promotion [ 35 ]. Epigenetic inactivation of RASSF1A by hypermethylation has been observed in various cancers, including HNC [ 36 ]. Our data showed that methylation of RASSF1A promoter led to a 7.69-fold increase in HNC risk compared to the control group.…”

Correlation between RASSF1A Methylation in Cell-Free DNA and the Prognosis of Cancer Patients: A Systematic Review and Meta-Analysis

“…CfDNAs are small fragments of DNA released from normal or tumor tissues as a result of cell apoptosis or necrosis and can be captured in large quantities in the blood [ 36 ]. It has been suggested that the concentration of cfDNA in the blood of cancer patients tends to be higher, because increased tumor size will promote cell apoptosis and necrosis, thus releasing a large amount of cfDNAs [ 37 ]. Furthermore, epigenetic biomarkers are stable and highly tissue specific in body fluids [ 38 ].…”

CNV Hotspots in Testicular Seminoma Tissue and Seminal Plasma

“…This CNV gain of KIT , as well as the CNV of KITLG reported here, may be related to the known activation of the KIT pathway in SE [ 41 ]. Next, RASSF1A is a tumour-suppressor gene, involved in the regulation of signalling pathways important for apoptosis, microtubule stability, and repression of the cell cycle [ 17 ]. RASSF1A was reported hypomethylated in SE and was concluded that its aberrant expression in SE is a consequence of aberrant DNA methylation [ 42 ].…”

“…MAGEC2 is a cancer-testis gene, for which disturbed protein expression is associated with SE [ 5 ]. RASSF1A is a tumour-suppressor gene whose methylation is altered in various cancers [ 17 ]. However, it is located on chr.…”