Detection of gene promoter hypermethylation in the tumor and serum of patients with gastric carcinoma.
OBJECTIVE
Aberrant promoter methylation, an alternative mechanism for gene silencing, is frequently detected in gastric cancer. We studied the feasibility of detecting aberrant methylation in serum of gastric cancer patients.


METHODS
Patients (54) with gastric adenocarcinoma were studied. The tumor and the paired serum were examined for aberrant methylation in DAP-kinase, E-cadherin, GSTP1, p15, and p16 by methylation-specific PCR. Serum from 30 age-matched noncancer patients was used as control.


RESULTS
Promoter methylation in DAP-kinase, E-cadherin, GSTP1, p15, and p16 were detected in 70.3, 75.9, 18.5, 68.5, and 66.7% of primary tumor. In serum of gastric cancer patients, methylation in DAP-kinase, E-cadherin, GSTP1, p15, and p16 were detected in 48.1, 57.4, 14.8, 55.6, and 51.9%, respectively. None of the control serum showed aberrant methylation. Aberrant methylation in serum DNA was all accompanied with methylation in the corresponding tumor samples. In general, >60% of serum from cancers with aberrant methylation demonstrated these epigenetic alterations.


CONCLUSIONS
Our findings suggest that aberrant promoter methylation in serum can be detected in a substantial proportion of gastric cancer patients, and this strategy should be evaluated in the screening and surveillance of gastric cancer.
Lee
Tin-Lap
TL
Department of Anatomical & Cellular Pathology, Prince of Wales Hospital, the Chinese University of Hong Kong, Shatin, Hong Kong SAR.
Leung
Wai K
WK
Chan
Michael W Y
MW
Ng
Enders K W
EK
Tong
Joanna H M
JH
Lo
Kwok-Wai
KW
Chung
S C Sydney
SC
Sung
Joseph J Y
JJ
To
Ka-Fai
KF
D000230:Adenocarcinoma / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins; D015820:Cadherins / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D016022:Case-Control Studies; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000097:blood*; D064550:Death-Associated Protein Kinases; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009367:Neoplasm Staging; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000378:metabolism; D025521:Tumor Suppressor Proteins
D051017:Apoptosis Regulatory Proteins; C493966:CDKN2B protein, human; D015820:Cadherins; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; D007527:Isoenzymes; D009363:Neoplasm Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases