Analysis on genetic instability and telomeric restriction fragment length of gastric cancer in vitro

Objective To explore the relationship of the telomere length to microsatellite instability (MSI) and to loss of heterozygosity (LOH) of APC, MCC and DCC genes in gastric carcinomas. Methods The specimens were collected from 68 cases of gastric cancer. The length of telomeric restriction fragment (TRF) was measured with Southern blot. LOH of APC, MCC and DCC genes, MSI and frameshift mutation of hMSH6, TGF βRⅡ and BAX genes were analyzed with PCR based methods. Results Among all 68 samples, MSI was found in 17 (25%), including 8 of MSI High (≥2 loci) and 9 of MSI Low (only one locus). The left 51 samples were found to be lacking MSI or microsatellite stability (MSS). Out of the 8 cases of MSI High, frameshift mutation of TGF βRⅡ, BAX and hMSH6 genes was showed in 6, 3 and 2 cases respectively, but no mutation of these genes was found in MSI Low and MSS samples. In 35 cases, including all MSI High and MSI Low studied for TRF, TRF length was shown to be shorter in 20 cases (57.1%), similar in 12 (34.3%) and elongated in 3 (8.6%). The mean TRF length had no correlation with clinicopatho logical parameters. No association was observed between TRF length and MSI or frameshift mutation. But LOH at the DCC locus were associated with telomere shortening ( P 0.01). This tendency was also observed in APC and MCC genes although there was no statistical significance. Conclusion The development of gastric cancer can occur through 2 different genetic pathways. In MSI High gastric cancers, defective mismatch repair leads the accumulation of mononucleotide mutation and the demostration of MSI High phenotype. In gastric cancers showing MSI Low or MSS, multiple deletions may represent the LOH pathway. Telomere erosion might participate in the LOH pathway but be unassociated with MSI High phenotype in gastric cancer.