ARUP Laboratories, Inc., Salt Lake City, UT, USA.
Clin Chem Lab Med. 2012 Oct 1;50(10):1707-21. doi: 10.1515/cclm-2011-0935.
Cellular DNA undergoes profound changes in methylation during cancer development, with hypermethylation occurring in specific gene promoters, amidst a backdrop of generalized hypomethylation. DNA methylation in cancer often causes the silencing of tumor suppressors and other genes important for cellular growth, regulation and differentiation. Over the past two decades, there have been thousands of publications describing the methylation status of hundreds of genes in cancer, with numerous associations with clinical states, disease outcomes and therapeutic responses being reported. New methods for DNA methylation fingerprinting have emerged, allowing for the exponential growth of "epigenomic" information. Despite this wealth of data, only a handful of methylated genes are utilized as cancer biomarkers in the clinical laboratory. A literature review centered on DNA methylation in six solid cancers was performed, including colorectal, pancreatic, prostate, bladder, breast and ovarian. Commonly methylated genes in the six cancer types were identified and catalogued, and could serve in the future as tissue-based biomarkers or as part of cancer-specific panels. Perhaps more importantly, this endeavor has also focused on methylated genes that appear to be unique to particular cancers. These genes may be more versatile for clinical use, with blood or urine-based cancer screening becoming a reality.
在癌症发展过程中，细胞 DNA 的甲基化会发生深刻变化，特定基因启动子的超甲基化伴随着广泛的低甲基化。癌症中的 DNA 甲基化通常会导致肿瘤抑制因子和其他对细胞生长、调节和分化重要的基因沉默。在过去的二十年中，已经有数千篇描述癌症中数百个基因甲基化状态的出版物，其中许多与临床状态、疾病结局和治疗反应有关。新的 DNA 甲基化指纹图谱方法已经出现，允许“表观基因组”信息呈指数增长。尽管有如此丰富的数据，但在临床实验室中，只有少数甲基化基因被用作癌症生物标志物。对包括结直肠癌、胰腺癌、前列腺癌、膀胱癌、乳腺癌和卵巢癌在内的六种实体癌中的 DNA 甲基化进行了文献综述。确定并编目了六种癌症类型中常见的甲基化基因，它们将来可以作为组织生物标志物或作为癌症特异性面板的一部分。也许更重要的是，这项工作还侧重于似乎是特定癌症所特有的甲基化基因。这些基因可能更适合临床应用，血液或尿液癌症筛查成为现实。
