Quantitative detection of promoter hypermethylation in multiple genes in the serum of patients with colorectal cancer.
OBJECTIVE
While promoter hypermethylation is a common molecular alteration of human colorectal cancer that could be detected in the bloodstream, we tested the feasibility of quantitative detection of aberrant DNA methylation in multiple genes in the serum samples of colorectal cancer patients.


METHODS
The pre-therapeutic serum samples of 49 colorectal cancer patients and 41 age-matched controls with normal colonoscopy were examined. The presence of methylated DNA in APC (adenomatous polyposis coli), hMLH1 (human MutL homolog 1), and HLTF (helicase-like transcription factor) was detected by quantitative methylation-specific PCR (MethyLight).


RESULTS
There was a significant difference in the concentration of methylated serum DNA between cancer patients and controls for HLTF (p= 0.015) and hMLH1 (p= 0.0001) genes, but not for APC gene (p= 0.21). In total, 28 patients with colorectal cancer and 4 controls had methylated DNA detected in at least one marker, which gave a sensitivity of 57% and specificity of 90%. All patients with methylation in two methylation markers had advanced (stage III/IV) cancer (p= 0.006) and patients with methylation in at least one marker tended to have a lower probability of survival (p= 0.08).


CONCLUSIONS
The quantitative detection of aberrant DNA methylation in serum may be a promising high-throughput approach for the noninvasive screening and monitoring of colorectal cancer.
Leung
Wai K
WK
Department of Medicine & Therapeutics, Prince of Wales Hospital, Shatin, Hong Kong.
To
Ka-Fai
KF
Man
Ellen P S
EP
Chan
Michael W Y
MW
Bai
Alfa H C
AH
Hui
Aric J
AJ
Chan
Francis K L
FK
Sung
Joseph J Y
JJ
D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D000369:Aged, 80 and over; D002352:Carrier Proteins; D015179:Colorectal Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000097:blood* / Q000235:genetics; D005240:Feasibility Studies; D005260:Female; D017491:Genes, APC / Q000502:physiology*; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000097:blood / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000097:blood / Q000235:genetics; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009363:Neoplasm Proteins / Q000097:blood* / Q000235:genetics; D009687:Nuclear Proteins / Q000097:blood* / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D014157:Transcription Factors / Q000097:blood* / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C100023:HLTF protein, human; D007527:Isoenzymes; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D000070957:MutL Protein Homolog 1