Protein tyrosine phosphatase receptor-like genes are frequently hypermethylated in sporadic colorectal cancer

Introduction: The activity of phosphatases could be influenced by genetic, as well as epigenetic alterations. In our study we have investigated the methylation status of four PTPRs: PTPRM, PTPRT, PTPRR and PTPRZ1, which were pre-selected using microarray techniques as being alternatively methylated in sporadic colorectal cancer. Materials and methods: The analyses were carried out on 131 surgical specimens obtained from sporadic colorectal cancer patients. The methylation status of the four genes was examined using MSP. Results: The analysis of promoter methylation using an Illumina 27K microarray revealed four protein tyrosine phosphatases PTPRM, PTPRT, PTPRR and PTPRZ1 as being hypermethylated with beta-value ≥ 0.2 and p≤0.05. Subsequent analysis using MSP confirmed these observations - the frequency of promoter methylation was significantly higher in tumor cells compared to matched normal tissue for each of the analyzed genes. There was no association observed between the methylation status of PTPRs and either CIMP, K-ras (codon 12) and BRAF (exon 15, V600E) mutations or tumor localization (proximal/distal). The results of our study show a statistically significant difference between promoter methylation in cancerous and healthy tissue. This result supports the hypothesis that the PTPR family plays an important role in the etiology of colorectal cancer.