Sakao Y, Noro M, Sekine S, Nozue M, Hirohashi S, Itoh T, Noguchi M
Department of Pathology, University of Tsukuba.
Jpn J Cancer Res. 1998 Oct;89(10):1020-7. doi: 10.1111/j.1349-7006.1998.tb00491.x.
We studied microsatellite instability (MI) and bax gene abnormalities in colorectal carcinomas from 36 patients diagnosed as having hereditary nonpolyposis colorectal cancers (HNPCC) according to the clinical criteria (12 with confirmed HNPCC in group A and 24 at high risk of HNPCC in group B) and from 20 randomly selected patients with other colorectal cancers. MI was examined at 4 dinucleotide microsatellite loci and one mononucleotide locus. Frameshift mutations in the bax gene were detected by polymerase chain reaction-single strand conformation polymorphism analysis. MI was detected in 7 of the 12 patients in group A and 12 of the 24 in group B. Three MI patterns were identified: type 1, MI in both mono- and dinucleotide repeats; type 2, MI only in mononucleotide repeats and type 3, MI only in dinucleotide repeats. Most MI-positive patients in group A showed type 1 MI, whereas in group B, 5 showed type 1, 3 showed type 2 and 4 showed type 3. Frameshift mutations in the bax gene correlated strongly with type 1 and type 2 MI. These results indicate that mutations of different DNA mismatch repair genes may cause several types of MI and result in several different clinical phenotypes of HNPCC. The bax gene may be one of the target genes which play a role in the tumorigenesis of HNPCC.
我们研究了36例根据临床标准诊断为遗传性非息肉病性结直肠癌（HNPCC）患者（A组12例确诊为HNPCC，B组24例有HNPCC高风险）以及20例随机选择的其他结直肠癌患者的微卫星不稳定性（MI）和bax基因异常情况。在4个二核苷酸微卫星位点和1个单核苷酸位点检测MI。通过聚合酶链反应-单链构象多态性分析检测bax基因的移码突变。A组12例患者中有7例检测到MI，B组24例中有12例检测到MI。识别出三种MI模式：1型，单核苷酸和二核苷酸重复序列均存在MI；2型，仅单核苷酸重复序列存在MI；3型，仅二核苷酸重复序列存在MI。A组大多数MI阳性患者表现为1型MI，而B组中，5例表现为1型，3例表现为2型，4例表现为3型。bax基因的移码突变与1型和2型MI密切相关。这些结果表明，不同的DNA错配修复基因突变可能导致几种类型的MI，并导致HNPCC的几种不同临床表型。bax基因可能是在HNPCC肿瘤发生中起作用的靶基因之一。
