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

应用微卫星标记D18S59、D18S476、D18S481、D18S52、D18S452和D18S57对177例正常大肠粘膜和相应的结直肠癌组织进行了18P杂合性缺失的检测。此外，在前面描述的条件下，通过聚合酶链式反应来确定存在于TS mRNA非翻译区的串联重复序列的数量。172例正常结肠黏膜中，90例为双重复(2R)/三重复(3R)TS基因。与90例2R/3R TS正常粘膜对照，共检测到58例18P等位基因缺失，包括TS基因座。2R/Lost和3R/Lost的TS基因缺失率分别为30%(12/40)和48%(19/40)。在2R/2R或3R/3R的癌组织中，包括TS基因座在内的等位基因丢失的频率与之相当。因此，TS基因不影响包括TS基因座在内的18P的杂合性缺失。用7种微卫星标记估计的18P在结直肠癌组织中丢失的程度是很大的。很难找到与结直肠癌发生有关的新基因(S)。无论18P丢失的程度如何，等位基因丢失都不影响TS基因的表达。TS基因3R阳性的结直肠癌组织中TS蛋白的表达显著升高。TS蛋白的高表达可能与TS基因的表达密切相关。

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.