Verma Mukesh, Seminara Daniela, Arena Fernando J, John Christy, Iwamoto Kumiko, Hartmuller Virginia
Analytic Epidemiology Research Branch, Epidemiology and Genetics Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, Rockville, Maryland 20852, USA.
Mol Diagn Ther. 2006;10(1):1-15. doi: 10.1007/BF03256438.
Gene expression patterns change during the initiation, progression, and development of cancer, as a result of both genetic and epigenetic mechanisms. Genetic changes arise due to irreversible changes in the nucleotide sequence, whereas epigenetic changes occur due to changes in chromatin conformation, histone acetylation, and methylation of the CpG islands located primarily in the promoter region of a gene. Both genetic and epigenetic markers can potentially be utilized to identify different stages of tumor development. Several such markers exhibit high sensitivity and specificity for different tumor types and can be assayed in biofluids and other specimens collected by noninvasive technologies. In spite of the availability of large numbers of diagnostic markers, only a few have been clinically validated so far. The current status and the challenges in the field of genetic and epigenetic markers in cancer diagnosis, risk assessment, and disease stratification are discussed.
由于遗传和表观遗传机制，基因表达模式在癌症的起始、进展和发展过程中会发生变化。遗传变化是由于核苷酸序列的不可逆变化而产生的，而表观遗传变化则是由于染色质构象、组蛋白乙酰化以及主要位于基因启动子区域的CpG岛甲基化的变化而发生的。遗传和表观遗传标记都有可能用于识别肿瘤发展的不同阶段。其中一些标记对不同肿瘤类型表现出高灵敏度和特异性，并且可以在通过非侵入性技术收集的生物流体和其他样本中进行检测。尽管有大量的诊断标记可供使用，但到目前为止只有少数几个经过了临床验证。本文讨论了癌症诊断、风险评估和疾病分层中遗传和表观遗传标记领域的现状及挑战。
