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.

中文翻译：

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表观遗传失活的 RASSF1A 作为肿瘤生物标志物。

RASSF1A 代表 RASSF1 基因的八种亚型之一。RASSF1A 是一种肿瘤抑制基因，其失活影响肿瘤的发生和发展。在癌症中，RASSF1A 经常因突变、杂合性丧失以及最常见的启动子高甲基化而失活。由于在各种癌症类型中检测到 RASSF1A 的表观遗传失活，因此对其进行了广泛的研究，如今，根据表观遗传的肿瘤生物标志物对 RASSF1A 启动子甲基化进行了研究。目前，对涉及致癌作用的基因（如 RASSF1A）的 DNA 甲基化的分析主要在基因组 DNA (gDNA) 上进行。同时，来自液体活检的无细胞 DNA (cfDNA) 最近已被开发为一种早期癌症诊断工具。本综述讨论了来自不同癌症类型的 gDNA 和 cfDNA 中异常甲基化的 RASSF1A 的证据及其在早期癌症诊断、预后和监测中的效用。此外，在各种癌症类型中比较了 gDNA 和 cfDNA 中 RASSF1A 的甲基化频率。讨论了上述调查的弱点和优势。总之，尽管 RASSSF1A 甲基化与癌症相关的重要性已经确立，并且它被包含在几个诊断小组中，但其诊断效用的证据仍处于实验阶段，尚未在标准临床医疗保健中实施。讨论了上述调查的弱点和优势。总之，尽管 RASSSF1A 甲基化与癌症相关的重要性已经确立，并且它被包含在几个诊断小组中，但其诊断效用的证据仍处于实验阶段，尚未在标准临床医疗保健中实施。讨论了上述调查的弱点和优势。总之，尽管 RASSSF1A 甲基化与癌症相关的重要性已经确立，并且它被包含在几个诊断小组中，但其诊断效用的证据仍处于实验阶段，尚未在标准临床医疗保健中实施。