Genome-wide analysis of aberrant DNA methylation for identification of potential biomarkers in colorectal cancer patients.
BACKGROUND
Colorectal cancer is one of the leading causes of mortality worldwide. Genome wide analysis studies have identified sequence mutations causing loss-of-function that are associated with disease occurrence and severity. Epigenetic modifications, such DNA methylation, have also been implicated in many cancers but have yet to be examined in the East Asian population of colorectal cancer patients.


METHODS
Biopsies of tumors and matched non-cancerous tissue types were obtained and genomic DNA was isolated and subjected to the bisulphite conversion method for comparative DNA methylation analysis on the Illumina Infinium HumanMethylation27 BeadChip.


RESULTS
Totals of 258 and 74 genes were found to be hyper- and hypo-methylated as compared to the individual's matched control tissue. Interestingly, three genes that exhibited hypermethylation in their promoter regions, CMTM2, ECRG4, and SH3GL3, were shown to be significantly associated with colorectal cancer in previous studies. Using heatmap cluster analysis, eight hypermethylated and 10 hypomethylated genes were identified as significantly differentially methylated genes in the tumour tissues.


CONCLUSIONS
Genome-wide methylation profiling facilitates rapid and simultaneous analysis of cancerous cells which may help to identify methylation markers with high sensitivity and specificity for diagnosis and prognosis. Our results show the promise of the microarray technology in identification of potential methylation biomarkers for colorectal cancers.
Department of Medical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Wei-Jia
WJ
Fang
Yi
Y
Zheng
Li-Ming
LM
Wu
Qing-Hong
QH
Ke
Hong
H
Shen
Ying
Y
Yuan
Shu-Sen
SS
Zheng
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D018925:Chemokines / Q000235:genetics; D016000:Cluster Analysis; D003106:Colon / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics*; D019175:DNA Methylation; D020869:Gene Expression Profiling; D015894:Genome, Human; D006801:Humans; D062792:MARVEL Domain-Containing Proteins / Q000235:genetics; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D012007:Rectum / Q000378:metabolism; D012680:Sensitivity and Specificity; D025521:Tumor Suppressor Proteins
D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; C505071:CMTM2 protein, human; D018925:Chemokines; C476999:ECRG4 protein, human; D062792:MARVEL Domain-Containing Proteins; D009363:Neoplasm Proteins; C115574:SH3GL3 protein, human; D025521:Tumor Suppressor Proteins