Jass J R, Edgar S
Department of Pathology, School of Medicine, University of Auckland, New Zealand.
Pathology. 1994 Oct;26(4):414-7. doi: 10.1080/00313029400169102.
DNA mismatch repair genes are responsible for the condition hereditary non-polyposis colorectal cancer (HNPCC). Genomic destabilization caused by failure of DNA mismatch repair leads to the progressive accumulation of somatic mutations and so to accelerated oncogenesis. The aim of this study was to document the rate of background mutational activity in the normal colorectal mucosa of subjects with HNPCC. A naturally occurring model utilizing a genetic polymorphism (O-acetyltransferase) allows the development of unicryptal loss of heterozygosity (LOH) to be detected by means of mild PAS histochemistry and quantified. The rate of unicryptal LOH was measured in informative and affected members of 3 HNPCC families and found to be within the expected range. This result is consistent with the finding that normal cells in HNPCC subjects are DNA repair proficient and supports the view that the mutational effects of the HNPCC gene occur selectively within adenomatous epithelium and serve to accelerate the adenoma-carcinoma sequence.
DNA错配修复基因与遗传性非息肉病性结直肠癌（HNPCC）的发病有关。DNA错配修复功能缺失导致的基因组不稳定会致使体细胞突变逐渐积累，进而加速肿瘤发生。本研究旨在记录HNPCC患者正常结直肠黏膜中的背景突变活性速率。利用一种自然发生的基因多态性（O-乙酰转移酶）模型，借助轻度PAS组织化学方法可检测并量化单隐窝杂合性缺失（LOH）的发生情况。在3个HNPCC家系的信息提供者和患病成员中测量了单隐窝LOH的发生率，结果发现其在预期范围内。这一结果与HNPCC患者正常细胞具有DNA修复能力的发现一致，支持了HNPCC基因的突变效应在腺瘤上皮内选择性发生并加速腺瘤-癌序列进展的观点。
