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.

我们使用Microsatellite标记D18S59，D18S476，D18S481，D18S52，D18S452和D18S57研究了177个正常结肠粘膜和相应的结肠直肠癌组织中染色体18p的杂合性丧失和相应的结直肠癌组织。此外，在其他地方描述的条件下，PCR确定了TS mRNA非翻译区域中存在的串联重复序列的数量。在172个正常结肠粘膜中，有90个显示了双重重复（2R）/三重复（3R）的TS基因型。观察到包括TS基因座在内的18p等位基因损失，与2R/3R TS基因型的90个正常粘膜相对应的58个样品。 2R/损失的TS基因座损失频率为30％（12/40），3R/损耗的频率为48％（19/40）。包括2R/2R或3R/3R的癌症组织（包括TS基因座）的等位基因损失的频率可比。因此，TS基因型不应影响包括TS基因座在内的18p的LOH。使用7种微卫星标记估算的结直肠癌组织中18p的损失程度非常宽。很难找到有助于结直肠癌致癌的新基因。不管18p的损失程度如何，等位基因损失不会影响TS mRNA或TS蛋白的表达。在具有3R的TS基因的结直肠癌组织中，TS蛋白的表达显着高。 TS mRNA的表达似乎显着促进了TS Protein的高表达。