Affiliations: Department of Molecular Genetics, Institute of
Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana,
Slovenia | Department of Abdominal Surgery, University Medical
Centre Ljubljana, Ljubljana, Slovenia | Institute of Biochemistry, Faculty of Medicine,
University of Ljubljana, Ljubljana, Slovenia
Note: [] Corresponding author: Prof. Metka Ravnik-Glavač,
Department of Molecular Genetics, Institute of Pathology, Faculty of Medicine,
University of Ljubljana, Zaloška 4, 1000 Ljubljana, Slovenia. Tel.: +386
0 1543 7183; Fax: +386 0 1543 7181; E-mail:
[email protected]
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 in TMEM25 in 69.2% (92/133) tumours analysed.
Furthermore, the expression of TMEM25 was found to be significantly lower in
tumour tissue. An inverse correlation between hypermethylation of TMEM25 and
TMEM25 down-regulated expression was observed. Our results suggest that epigenetic down-regulation of TMEM25 is
cancer-related; we thus suggest that TMEM25 hypermethylation might play a
significant role in altering expression of this gene in colorectal cancer.
