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Investigation of the significance of the loss of 18p which is frequently observed in colorectal cancer tissue.

研究结直肠癌组织中常见的 18p 缺失的重要性。

基本信息

批准号：
14370381
负责人：
OMURA Kenji
金额：
$ 8.51万
依托单位：
KANAZAWA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370381/
关键词：
colorectal cancer chromosome 18 loss of heterozygosity allelic loss microsatellite marker thymidylate synthase polymerase chain reaction gene polymorphism complementary DNA loss of heterogeneity 癌抑制遺伝子

项目摘要

We examined the loss of heterozygosity of chromosome 18p in 177 normal colonic mucosa and corresponding colorectal cancer tissue by PCR using microsatellite markers D18S59,D18S476,D18S481,D18S52,D18S452 and D18S57. Furthermore, the number of the tandem repeat sequences existing in the non-translational region of the TS mRNA was determined by the PCR under the conditions described elsewhere. Of 172 normal colonic mucosa, 90 showed the TS genotype of double repeat(2R)/triple repeat(3R). The 18p allelic loss, including TS locus, was observed 58 samples corresponding to the 90 normal mucosa of 2R/3R TS genotype. The frequency of the loss of TS locus was 30%(12/40) for 2R/loss, and 48%(19/40) for 3R/loss. The frequency of allelic loss including TS locus is comparable for the cancer tissues with 2R/2R or 3R/3R. Consequently, the TS genotype should not affect the LOH of 18p including TS locus. The extent of the loss of 18p in colorectal cancer tissue estimated using 7 kinds of microsatellite markers was very wide. It was quite difficult to find new gene(s) contributing to the carcinogenesis of colorectal cancer. The allelic loss did not affect the expression of TS mRNA or TS protein, regardless the extent of the loss of 18p. The expression of TS protein was significantly high in the colorectal cancer tissue which had TS gene with 3R. It seemed that the expression of TS mRNA significantly contributed to the high expression of TS prortein.

应用微卫星标记D18 S59、D18 S476、D18 S481、D18 S52、D18 S452和D18 S57对177例正常结肠粘膜和相应大肠癌组织进行了18号染色体p杂合性缺失的检测。此外，在其他地方描述的条件下，通过PCR确定TS mRNA的非翻译区中存在的串联重复序列的数量。在172例正常结肠粘膜中，90例为TS基因型，均为双重复（2 R）/三重复（3R）。在90例2 R/3R TS基因型正常粘膜中，有58例出现18 p等位基因缺失，其中包括TS位点。TS位点2 R/丢失的丢失率为30%（12/40），3R/丢失的丢失率为48%（19/40）。在2 R/2 R和3R/3R的癌组织中，包括TS位点在内的等位基因丢失频率相当。因此，TS基因型不应影响18 p（含TS）位点的洛丢失。7种微卫星标记在大肠癌组织中18 p缺失的范围很广。发现新的与大肠癌发生有关的基因是相当困难的。无论18 p缺失的程度如何，等位基因缺失均不影响TS mRNA或TS蛋白的表达。TS蛋白在携带3R的TS基因的大肠癌组织中表达显著增高。TS蛋白的高表达可能与TS mRNA的表达有关。