Abstract
The identification of novel genes involved in colorectal cancerogenesis is of high clinical relevance for early diagnosis, applying new therapeutic strategies and monitoring disease recurrence, in order to reduce disease incidence and mortality. Gene silencing through CpG island hypermethylation is a major epigenetic mechanism involved in cancer development. In our study, we aimed to identify and validate novel genes with a tumour specific DNA methylation profile in colorectal cancer. We performed a whole-genome methylation scan and identified several possible candidate genes that are hypermethylated in tumour in comparison to healthy colon mucosa. Using methylation-specific high-resolution melting analysis in a set consisting of 133 colorectal cancer samples, we were able to confirm an altered CpG site inTMEM25in 69.2% (92/133) tumours analysed. Furthermore, the expression ofTMEM25was found to be significantly lower in tumour tissue. An inverse correlation between hypermethylation ofTMEM25andTMEM25down-regulated expression was observed.Our results suggest that epigenetic down-regulation ofTMEM25is cancer-related; we thus suggest thatTMEM25hypermethylation might play a significant role in altering expression of this gene in colorectal cancer.
Highlights
Colorectal cancer (CRC) is one of the most commonly diagnosed human malignancies worldwide, with a disease-specific mortality rate close to 33% [1]
Our results suggest that epigenetic down-regulation of transmembrane 25 gene (TMEM25) is cancer-related; we suggest that TMEM25 hypermethylation might play a significant role in altering expression of this gene in colorectal cancer
It arises as a consequence of the accumulation of genetic alterations and epigenetic alterations
Summary
Colorectal cancer (CRC) is one of the most commonly diagnosed human malignancies worldwide, with a disease-specific mortality rate close to 33% [1]. It arises as a consequence of the accumulation of genetic alterations (such as gene mutations, gene amplifications etc.) and epigenetic alterations (such as aberrant DNA methylation, chromatin modifications etc.) [2]. Changes in DNA methylation have been reported to occur early in CRC development and are promising as early diagnostic markers [8]. Several epigenetic markers have been discovered in CRC tumours, including
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