Genome-wide Analysis of Aberrant DNA Methylation for Identification of Potential Biomarkers in Colorectal Cancer Patients

Abstract

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.

GWAS of five gynecologic diseases and cross-trait analysis in Japanese

“…Rs145152209:A > G at SH3GL3/BNC1 locus is associated with UF. SH3GL3 and BNC1 are both neither reported in the context of UF, however, SH3GL3 is reported as a colorectal cancer-associated gene [43], and BNC1 is reported to have association with pancreatic cancer [44,45]. These suggest that this locus may play an role in proliferative property of UF in some undetermined mechanisms.…”

Lack of Prognostic Significance of SOCS-1 Expression in Colorectal Adenocarcinomas

“…The most important prognostic indicators in CRC patients include tumor stage and prognostic or predictive markers (Wolpin and Mayer Colussi et al, 2013;Yang et al, 2014). Candidate markers include blood antigens and circulating tumor cells, tumor enzymes and gene expressions (Denlinger and Cohen 2007;Zlobec and Lugli 2008;Chan et al, 2010;Firestein et al, 2010;Imamura et al, 2012;Shima et al, 2011;Fang et al, 2012;Liao et al, 2012;Morikawa et al, 2012;Dong et al, 2013;Li et al, 2013). However, useful prognostic factors related with tumor stage and clinical outcomes of such patients have not been well characterized.…”

Epigenomic Analysis of Sézary Syndrome Defines Patterns of Aberrant DNA Methylation and Identifies Diagnostic Markers

“…Sz-specific methylation of these selectively hypermethylated gene promoters, and CMTM2 in particular, renders them useful epigenetic markers for the diagnosis of this lymphoid malignancy. The CMTM2 (chemokine-like factor MARVEL transmembrane domain-containing 2) gene belongs to the chemokine-like factor superfamily and is primarily expressed in testis, bone marrow, and peripheral blood cells (Fang et al, 2012). CMTM2 affects the function of the cyclic AMP response element-binding protein (AP-1) and CRE-binding protein (CREB) transcription factors in T cells (Song et al, 2010).…”