17号染色体短臂等位基因缺失、p53基因的突变以及左右侧结直肠癌中的微卫星不稳定性。

Allelic loss of chromosome 17p, mutation of the p53 gene, and microsatellite instability in right- and left-sided colorectal cancer.

作者信息

Watatani M, Yoshida T, Kuroda K, Ieda S, Yasutomi M

机构信息

First Department of Surgery, Faculty of Medicine, Kinki University, Osakasayama, Japan.

出版信息

Cancer. 1996 Apr 15;77(8 Suppl):1688-93. doi: 10.1002/(SICI)1097-0142(19960415)77:8<1688::AID-CNCR40>3.0.CO;2-T.

DOI:10.1002/(SICI)1097-0142(19960415)77:8<1688::AID-CNCR40>3.0.CO;2-T

PMID:8608563

Abstract

BACKGROUND

Epidemiologic and genetic studies suggest that cancer of the right and left sides of the bowel arise through different mechanisms. To investigate the molecular mechanisms, allelic loss of chromosome 17p, p53 mutations, and microsatellite instability were analyzed in colorectal cancer according to tumor site.

METHODS

Using the polymerase chain reaction and single strand conformation polymorphism (PCR-SSCP) method, mutations within exons 5-8 of the p53 gene were examined in 108 colorectal cancers including 30 right-sided and 78 left-sided colorectal cancers. Allelic loss of chromosome 17p was studied by restriction fragment length polymorphism analysis, and genetic instability was examined for replication error (RER) at three microsatellite loci on chromosomes 2p, 17p, and 17q.

RESULTS

Allelic loss was observed in 61% (14 of 23 informative cases) of right-sided tumors and in 60% (26 of 43 informative cases) of left-sided tumors. PCR-SSCP analysis demonstrated that 63 of 108 tumors had a mutated p53 gene in exons 5, 6, 7, or 8. When comparing the frequency of mutation in each exon based on tumor site, the frequency of mutation in exon 8 in right-sided (2 of 18 informative cases) tumors was significantly lower than that observed in left-sided (17 of 45 informative cases) tumors. RER(+) was observed in 43% of right-sided tumors, whereas 24% of left-sided tumors were RER(+). Although the difference was not statistically significant, a trend was observed between RER(+) phenotype and tumor site.

CONCLUSIONS

Our results suggest that the molecular mechanisms of colorectal carcinogens may differ between right- and left-sided tumors.

摘要

背景

流行病学和遗传学研究表明，肠道左右两侧的癌症是通过不同机制产生的。为了研究其分子机制，根据肿瘤部位分析了17号染色体短臂的等位基因缺失、p53基因突变和微卫星不稳定性。

方法

采用聚合酶链反应和单链构象多态性（PCR-SSCP）方法，检测了108例结直肠癌（包括30例右侧和78例左侧结直肠癌）中p53基因第5至8外显子的突变情况。通过限制性片段长度多态性分析研究17号染色体短臂的等位基因缺失，并检测2号染色体、17号染色体短臂和17号染色体长臂上三个微卫星位点的复制错误（RER）以评估基因不稳定性。

结果

右侧肿瘤中61%（23例信息充分病例中的14例）观察到等位基因缺失，左侧肿瘤中60%（43例信息充分病例中的26例）观察到等位基因缺失。PCR-SSCP分析显示，108例肿瘤中有63例在第5、6、7或8外显子中有p53基因突变。根据肿瘤部位比较每个外显子的突变频率时，右侧肿瘤（18例信息充分病例中的2例）第8外显子的突变频率显著低于左侧肿瘤（45例信息充分病例中的17例）。43%的右侧肿瘤观察到RER(+)，而24%的左侧肿瘤为RER(+)。虽然差异无统计学意义，但在RER(+)表型与肿瘤部位之间观察到一种趋势。