Tong Yu Kwan, Lo Yuk Ming Dennis
Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, China.
Front Biosci. 2006 Sep 1;11:2647-56. doi: 10.2741/1998.
Successful detection of circulating nucleic acids has opened up new possibilities in cancer testing and prenatal diagnosis. Circulating DNA markers are useful in cancer detection, prognostication and monitoring. Cancer-associated molecular changes which can be detected include gene mutations, chromosomal rearrangements, microsatellite alterations, viral sequences, and, to be discussed in more detailed, gene promoter hypermethylation. Methylation analysis is commonly performed by DNA digestion with methylation-sensitive restriction endonucleases followed by polymerase chain reaction (PCR), or bisulfite modification followed by methylation-specific PCR (MSP). The detection of fetal DNA in maternal plasma has opened up new possibilities for noninvasive prenatal diagnosis. However, circulating fetal DNA detection has been based on exploiting gender and polymorphic differences between the fetus and mother. The recent discovery of epigenetic differences between the maternal and the fetal DNA detectable in maternal plasma has launched a hunt for fetal-derived epigenetic markers in maternal plasma. It is hoped that this type of universally applicable markers would be made available in a clinical diagnostic setting in the near future.
循环核酸的成功检测为癌症检测和产前诊断开辟了新的可能性。循环DNA标志物在癌症检测、预后评估和监测中很有用。可检测到的与癌症相关的分子变化包括基因突变、染色体重排、微卫星改变、病毒序列，以及将更详细讨论的基因启动子高甲基化。甲基化分析通常通过用甲基化敏感的限制性内切酶消化DNA，然后进行聚合酶链反应（PCR），或通过亚硫酸氢盐修饰，然后进行甲基化特异性PCR（MSP）来进行。母血中胎儿DNA的检测为无创产前诊断开辟了新的可能性。然而，循环胎儿DNA的检测一直基于利用胎儿和母亲之间的性别和多态性差异。最近在母血中可检测到的母源和胎儿DNA之间表观遗传差异的发现，引发了在母血中寻找胎儿来源的表观遗传标志物的热潮。希望这种普遍适用的标志物在不久的将来能用于临床诊断。
