Heinen C D, Shivapurkar N, Tang Z, Groden J, Alabaster O
Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, Ohio 45267-0524, USA.
Cancer Res. 1996 Dec 1;56(23):5339-41.
Aberrant crypt foci (ACF) are distinct microscopic lesions of the colon thought to be the earliest identifiable precursors of colon cancer. As precursors of colon cancer, ACF may contain mutations in genes that are altered early in colorectal tumorigenesis. Candidates for these genes include APC, K-Ras, and those of the DNA mismatch repair system. Some colon cancers with mutations in DNA mismatch repair genes are characterized by genomic instability at simple repeated sequences, also known as microsatellite instability. In this study, we analyzed 19 ACF (> or = 20 crypts/focus) and adjoining, microscopically normal colonic mucosa from 10 colon cancer patients for the presence of microsatellite instability. DNA from two ACF from two different patients displayed microsatellite instability. None of the DNA samples from normal mucosa displayed microsatellite instability. These observations support the role of ACF as a precursor to colon cancer and provide some evidence that mutations in DNA mismatch repair genes are early somatic events in colon cancer.
异常隐窝灶（ACF）是结肠明显的微观病变，被认为是结肠癌最早可识别的前体。作为结肠癌的前体，ACF可能含有在结直肠癌发生早期就发生改变的基因中的突变。这些基因的候选者包括APC、K-Ras以及DNA错配修复系统的基因。一些DNA错配修复基因突变的结肠癌的特征是简单重复序列处的基因组不稳定，也称为微卫星不稳定。在本研究中，我们分析了来自10例结肠癌患者的19个ACF（≥20个隐窝/灶）以及相邻的显微镜下正常结肠黏膜，以检测微卫星不稳定的存在。来自两名不同患者的两个ACF的DNA显示出微卫星不稳定。正常黏膜的DNA样本均未显示微卫星不稳定。这些观察结果支持ACF作为结肠癌前体的作用，并提供了一些证据表明DNA错配修复基因突变是结肠癌早期的体细胞事件。
