Link between dysregulated hypoxia signaling and aberrant methylation in clear cell renal cell carcinoma？

Dysregulated pseudo-hypoxia （through its effects on cell survival, angiogenesis, metabolism, invasion） and epigenetic dysregulation [through widespread suppression of tumor suppressor genes involved in cell cycle, apoptosis, adhesion, immune evasion, etc. （1）] are considered to be the two central driving pathogenic features in the progression of clear cell Renal Cell Carcinoma （ccRCC） （2,3）.

Aberrant DNA Methylation in Human Cancers

DNA methylation, one of the best-characterized epigenetic modifications, plays essential roles in diseases, including human cancers. In recent years, our understanding on DNA methylation with human cancers has made significant progress, which was facilitated by stunning development in the analysis of the human methylome of multiple cancer types. In this review, recent developments in the characterization of aberrant DNA methylation involved in human cancers development were discussed with special emphasis on the mechanisms of aberrant DNA methylation in human cancers. We also summarize the recent treatment strategy for human cancers with de-methylation drugs.

Relationship between methylation and colonic inflammation in inflammatory bowel disease

AIM:To investigate the relationship between the methylation status in the SLIT2 and TGFB2 promoters and colonic inflammation in inflammatory bowel disease patients.METHODS:We evaluated the methylation status of 2genes(SLIT2 and TGFB2)in 226 biopsies taken from62 colonoscopies of 38 patients(29 ulcerative colitis and 9 Crohn’s colitis)using methylation-specific melting curve analysis.The relationships between methylation status and clinical,biological,endoscopic and histological activities were evaluated.Twenty-three of the 38patients had a second colonoscopy and were included in a longitudinal analysis.Numerical results were given as the means±SD of the sample and range,except when specified.Student t analysis,U Mann Whitney and ANOVA factor were used to compare the means.Qualitative results were based on theχ2 test.RESULTS:SLIT2 methylation was more frequent in samples with endoscopic activity than with endoscopic remission(55%vs 18%,P<0.001).SLIT2 methylation was also higher in samples with acute inflammation(56.5%)than in samples with chronic(24%)or absent inflammation(15%)(P<0.001).For TGFB2methylation,the correlation was only significant with endoscopic activity.Methylation was higher in the distal colon for both genes(P<0.001 for SLIT2 and P=0.022for TGFB2).In the multivariate analysis,only inflammation status(and not disease duration or extension)was independently associated with SLIT2 methylation[OR=6.6(95%CI:1.65-27.36),P=0.009].In the longitudinal analysis,the maintenance of endoscopic remission was protective for methylation.CONCLUSION:Endoscopic and histological inflammation are predictive for SLIT2 methylation.