PT  - JOURNAL ARTICLE
AU  - Wang, Dong
AU  - Geng, Xin
AU  - Li, Yanyun
AU  - Wang, Yuchuan
AU  - Li, Yanni
AU  - Zhao, Linsheng
AU  - Zhang, Weiming
TI  - Detection of Frameshift Mutations of the Transforming Growth Factor β Receptor II in Gastric Cancers with Microsatellite Instability
DP  - 2006 Aug 01
TA  - Chinese Journal of Clinical Oncology
PG  - 267--272
VI  - 3
IP  - 4
4099  - http://www.cancerbiomed.org/content/3/4/267.short
4100  - http://www.cancerbiomed.org/content/3/4/267.full
SO  - Cancer Biol Med2006 Aug 01; 3
AB  - OBJECTIVE To study the relationship among microsatellite instability (MSI), frameshift mutations (FM) of the transforming growth factor β receptor II (TGFβR II), méthylation state of the hMLFU promoter and hMLFU protein expression level In gastric cancers, and to explore their relationship to gastric carcinogenesis.METHODS DNA was isolated from 101 gastric specimens and 5 microsatelllte loci were detected. PCR, electrophoresis on denatured polyacrylamide gels and silver staining were performed to detect the MSI. The FMs of TGFβR II were also screened with the same method. HMLFU méthylation was analyzed by méthylation specific PCR (MSP) and sequencing. HMLH1 protein expression was detected using immunohistochemistry.RESULTS The Incidence of MSIs was 53.7% and 0% in the cancers and normal tissues, respectively, with the frequency of MSIs being significantly higher in the gastric cancers compared to the normal gastric tissues (P<0.05). The frequency of hMLH1 méthylation was 41.5% (17/41 ) in the gastric cancers and 0%(0/60) in the normal group. Decreased hMLH1 expression was observed In 94.1%(16/17) of cases exhibiting méthylation. FMs of TGFβR II were Identified in 5 (62.5%) of the 8 samples with MSIH. In contrast, FMs were not found in MSI-L or microsatellite stable (MSS) cases.CONCLUSION MSIs and FMs of TGFβR II may play an important role In gastric carcinogenesis. HMLH1 méthylation is an important modification of the DNA which results in inactivation of hMLH1 and mismatch repair defects which lead to MSIs and FMs of TGFβR II.