TY - JOUR
T1 - Promoter methylation and silencing of PTEN in gastric carcinoma
AU - Kang, Young Hwa
AU - Lee, Hye Seung
AU - Kim, Woo Ho
PY - 2002
Y1 - 2002
N2 - The PTEN/MMAC1/TEP1 gene (phosphatase and tensin homolog deleted on chromosome 10/mutated in multiple advanced cancers/TGF-β regulated and epithelial cell enriched phosphatase 1), which regulates the signaling pathways of Akt, is a novel tumor suppressor gene implicated in multiple cancers. Because a number of tumor suppressor genes are known to be silenced by aberrant promoter methylation, we examined the methylation status of the 5′ CpG islands of PTEN using methylation-specific PCR. The altered expression of PTEN in 310 gastric carcinomas was analyzed by immunohistochemical staining using tissue-array and clinicopathologic profiles related to PTEN expression were characterized. Of 310 consecutive gastric carcinomas, 62 cases (20%) showed expression loss of PTEN. Altered PTEN expression was significantly associated with tumor depth and size, lymphatic invasion, advanced stage, pTNM stage, and patient survival (p < 0.001). The promoter methylation frequency of PTEN was found to be present in 26 (39%) of 66 cases examined, and 19 (73%) of 26 gastric cancer tissues showing promoter methylation exhibited the loss of PTEN expression. Abnormalities in the expression of PTEN significantly correlated with promoter methylation (p < 0.001). In conclusion, silencing of the PTEN gene occurs frequently in gastric carcinoma and aberrant promoter methylation is a major mechanism of silencing of the PTEN gene. The abnormalities of the PTEN gene are associated with tumor progression, metastasis, and survival.
AB - The PTEN/MMAC1/TEP1 gene (phosphatase and tensin homolog deleted on chromosome 10/mutated in multiple advanced cancers/TGF-β regulated and epithelial cell enriched phosphatase 1), which regulates the signaling pathways of Akt, is a novel tumor suppressor gene implicated in multiple cancers. Because a number of tumor suppressor genes are known to be silenced by aberrant promoter methylation, we examined the methylation status of the 5′ CpG islands of PTEN using methylation-specific PCR. The altered expression of PTEN in 310 gastric carcinomas was analyzed by immunohistochemical staining using tissue-array and clinicopathologic profiles related to PTEN expression were characterized. Of 310 consecutive gastric carcinomas, 62 cases (20%) showed expression loss of PTEN. Altered PTEN expression was significantly associated with tumor depth and size, lymphatic invasion, advanced stage, pTNM stage, and patient survival (p < 0.001). The promoter methylation frequency of PTEN was found to be present in 26 (39%) of 66 cases examined, and 19 (73%) of 26 gastric cancer tissues showing promoter methylation exhibited the loss of PTEN expression. Abnormalities in the expression of PTEN significantly correlated with promoter methylation (p < 0.001). In conclusion, silencing of the PTEN gene occurs frequently in gastric carcinoma and aberrant promoter methylation is a major mechanism of silencing of the PTEN gene. The abnormalities of the PTEN gene are associated with tumor progression, metastasis, and survival.
UR - http://www.scopus.com/inward/record.url?scp=0036127525&partnerID=8YFLogxK
U2 - 10.1038/labinvest.3780422
DO - 10.1038/labinvest.3780422
M3 - Article
C2 - 11896207
AN - SCOPUS:0036127525
SN - 0023-6837
VL - 82
SP - 285
EP - 291
JO - Laboratory Investigation
JF - Laboratory Investigation
IS - 3
ER -
