Telomere erosion is independent of microsatellite instability but related to loss of heterozygosity in gastric cancer.
OBJECTIVE
To correlate the length of the telomere to microsatellite instability (MSI) and loss of heterozygosity (LOH) of APC, MCC and DCC genes in gastric carcinomas.


METHODS
Telomeric restriction fragment (TRF) length of gastric cancer was measured with Southern blot. LOH of APC, MCC and DCC genes, microsatellite instability (MSI) and frameshift mutation of hMSH6, TGF-betaRII and BAX genes were analyzed by PCR-based methods.


RESULTS
Sixty-eight cases of sporadic gastric carcinoma were studied for MSI using five microsatellite markers. MSI in at least one locus was detected in 17 (25%) of 68 tumors analyzed. Frameshift mutations of hMSH6, TGF-betaRII and BAX were detected in 2,6 and 3 of gastric carcinomas respectively showing high MSI (> or = 2 loci, n = 8), but none was found in those showing low MSI (only one locus, n = 9) or MSS (tumor lacking MSI or stable, n = 51). Thirty-five cases, including all high MSI and low MSI, were studied for TRF. The mean TRF length was not correlated with clinicopathological parameters. No association was observed between TRF length and MSI or frameshift mutation. On the contrary, LOH at the DCC locus was related to telomere shortening (P<0.01). This tendency was also observed in APC and MCC genes, although there was no statistical significance.


CONCLUSIONS
The development of gastric cancer can arise through two different genetic pathways. In high MSI gastric cancers, defective mismatch repair allows mutations to accumulate and generate the high MSI phenotype. In gastric cancers showing either low MSI or MSS, multiple deletions may represent the LOH pathway. Telomere erosion is independent of high MSI phenotype but related to the LOH pathway in gastric cancer.
Fang
D C
DC
Southwest Hospital Third Military Medical University, Chongqing 400038,China. fangdianchun@hotmail.com
Yang
S M
SM
Zhou
X D
XD
Wang
D X
DX
Luo
Y H
YH
D000328:Adult; D000368:Aged; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D016615:Telomere / Q000473:pathology*
D004273:DNA, Neoplasm