Screening of New Tumor Suppressor Genes in Sporadic Colorectal Cancer Patients

Background/Aims: The generation mechanism of colorectal. cancer (CRC) has not been revealed completely, and it is believed that some unknown tumor-related genes were involved in CRC. The purpose of this study was to screen for unknown tumor suppressor genes (TSGs) in patients with sporadic CRC. Methodology: Through loss of heterozygosity (LOH) analysis on chromosome 10 in sporadic CRC, we have found that D10S185 (10q23.31-24.33) exhibited a higher LOH frequency in our previous study. In this study, seven polymorphic microsatellite markers were chosen for refined LOH mapping of 10q23.31-24.33 in 83 Chinese patients with sporadic CRC. Based on refined LOH mapping, 51 genes were selected for the microarray-based high throughput screening which was done to identify new genes that are CRC-related. Microarray results were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Results: We found that the average LOH frequency of 10q23.31-24.33 was 35.53%, and that the LOH frequency of D10S1265 correlated to Dukes stage. Through the microarray-based high throughput screening, we found 4 significant down-regulated genes: PLCE1, CPEB3, NEX2-3 and SEMA4G. And the down-regulation of PLCE1 was most significant. The results of qRT-PCR also showed that the expression of PLCE1 was at low levels in cancer tissues compared with normal tissues. It was in relative agreement with the DNA microarray data. Conclusions: This study demonstrated that PLCE1 might be a new tumor suppressor gene related to sporadic colorectal cancer. Further studies should be done to prove it.