RT Journal Article
SR Electronic
T1 Detection of Frameshift Mutations of the Transforming Growth Factor β Receptor II in Gastric Cancers with Microsatellite Instability
JF Chinese Journal of Clinical Oncology
JO Cancer Biol Med
FD China Anti-Cancer Association
SP 267
OP 272
VO 3
IS 4
A1 Wang, Dong
A1 Geng, Xin
A1 Li, Yanyun
A1 Wang, Yuchuan
A1 Li, Yanni
A1 Zhao, Linsheng
A1 Zhang, Weiming
YR 2006
UL http://www.cancerbiomed.org/content/3/4/267.abstract
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.