Human urine contains small, 150 to 250 nucleotide-sized, soluble DNA derived from the circulation and may be useful in the detection of colorectal cancer
Human urine contains small, 150 to 250 nucleotide-sized, soluble DNA derived from the circulation and may be useful in the detection of colorectal cancer
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DOI：
10.1016/s1525-1578(10)60497-7
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发表时间：
2004-05-01
影响因子：
4.1
通讯作者：
Block, TM
中科院分区：
文献类型：
--
作者：
Su, YH;Wang, MJ;Block, TM
人类尿液已被证明含有每毫升亚微克的DNA。我们在这里表明，从人尿中分离的DNA分为两种大小：大的物种，大于1 kb，主要是细胞相关的，大小不一；小的物种，在150到250 bp之间，主要是非细胞相关的。我们通过比较从肿瘤、血液和结直肠癌（CRC）患者的尿液中分离的DNA中存在的突变K-ras序列，发现低分子量的尿DNA来源于循环，这些DNA中含有K-ras原癌基因密码子12突变。在尿液中，突变的K-ras序列在低分子量物种中大量存在，但在大分子质量衍生的DNA中却很少。最后，一项盲法研究探讨了在尿液DNA中检测突变K-ras序列与含有突变K-ras的结直肠癌和息肉的诊断相关的可能性。当对20例结直肠癌或腺瘤性息肉患者的尿液和组织切片进行K-ras突变分析时，在同一个体的尿液及其相应的疾病组织中检测到突变DNA的一致性为83%。经肾DNA的来源可能是凋亡细胞，并讨论了这一发现在癌症检测和监测中的潜在用途。
Human urine has been shown to possess submicrogram per milliliter amounts of DNA. We show here that DNA isolated from human urine resolves into two size categories: the large species, greater than I kb, being predominantly cell associated and heterogeneous in size, and the smaller, between 150 to 250 bp, being mostly non-cell associated. We showed that the low molecular weight class of urine DNA is derived from the circulation, by comparing the mutated K-ras sequences present in DNA isolated from tumor, blood, and urine derived from an individual with a colorectal carcinoma (CRC) containing a mutation in codon 12 of the K-ras proto-oncogene. in the urine, mutated K-ras sequences were abundant in the low molecular weight species, but far less abundant in the large molecular weight-derived DNA. Finally, the possibility that detection of mutant K-ras sequences in DNA derived from the urine correlates with the occurrence of a diagnosis of CRC and polyps that contain mutant K-ras was explored in a blinded study. There was an 83% concurrence of mutated DNA detected in urine and its corresponding disease tissue from the same individuals, when paired urine and tissue sections from 20 subjects with either CRC or adenomatous polyps were analyzed for K-ras mutation. The possibility that the source of the trans renal DNA is apoptotic cells, and the potential use of this finding for cancer detection and monitoring is discussed.