Augenlicht L H, Richards C, Corner G, Pretlow T P
Department of Oncology, Albert Einstein Cancer Center, Bronx, New York 10467, USA.
Oncogene. 1996 Apr 18;12(8):1767-72.
Aberrant crypt foci (ACF) are morphologically abnormal structures that can be identified in whole amounts of colonic tissue from rodents treated with colon carcinogens and from patients at risk for development of colon tumors. ACF are heterogeneous and exhibit properties, such as altered patterns of cell proliferation, the presence of dysplasia, and mutations in protooncogenes and tumor formation. In this study, we have investigated the presence of genomic instability in DNA isolated from human ACF from patients with colon cancer. Altered allele length detected by electrophoretic separation of PCR amplified oligo A or microsatellite loci was used to identify candidate samples which were then more rigorously investigated by sequence analysis for instability. Of 20 patients examined, two exhibited alterations at two loci, and this instability could be confirmed by sequence analysis. An additional seven of the 20 patients had evidence for instability at a single locus. Quantitative sequence analysis of the DNA from an ACF of one of these seven patients was consistent with alteration of allele length in this patient, but the alteration was not sufficiently different from normal to reach statistical significance. Thus, genomic instability, manifest as altered length of microsatellite and oligo A sequences, in present in some ACF, and therefore can be a very early event in the development of some human colon cancers.
异常隐窝灶（ACF）是形态学上异常的结构，可在经结肠癌致癌物处理的啮齿动物以及有患结肠肿瘤风险的患者的整个结肠组织中识别出来。ACF具有异质性，并表现出一些特性，如细胞增殖模式改变、发育异常的存在、原癌基因突变以及肿瘤形成。在本研究中，我们调查了从结肠癌患者的人类ACF中分离的DNA中基因组不稳定性的存在情况。通过对PCR扩增的寡聚A或微卫星位点进行电泳分离检测到的等位基因长度改变，用于识别候选样本，然后通过序列分析对其进行更严格的不稳定性研究。在检查的20名患者中，两名患者在两个位点出现改变，这种不稳定性可通过序列分析得到证实。在这20名患者中，另外7名患者在单个位点有不稳定性证据。对这7名患者中一名患者的ACF的DNA进行定量序列分析，结果与该患者等位基因长度改变一致，但这种改变与正常情况的差异不足以达到统计学意义。因此，基因组不稳定性表现为微卫星和寡聚A序列长度改变，存在于一些ACF中，因此可能是某些人类结肠癌发生过程中非常早期的事件。
