Abstract
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 (CRC). The analyses were carried out on 131 surgical specimens obtained from sporadic CRC patients. The methylation status of the four genes was examined using methyl specific PCR (MSP). The analysis of promoter methylation using an Illumina 27K microarray revealed four protein tyrosine phosphatases PTPRM, PTPRT, PTPRR and PTPRZ1 as being hypermethylated with β-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 with 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 has an important role in the etiology of CRC.
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Acknowledgements
This paper has been supported by the State Committee for Scientific Research, Polish Ministry for Scientific Research and Information Technology (grant no. N N401 601438), 2010–2013 and by a research fellowship within the ‘Development Program of Wroclaw Medical University’ funded by the European Social Fund, Human Capital, National Cohesion Strategy ‘(contract no. UDA-POKL 04.01.01-00-010/08-00)’. David Ramsey is supported by Science Foundation Ireland under the BIO-SI project (no. 07MI012).
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Laczmanska, I., Karpinski, P., Bebenek, M. et al. Protein tyrosine phosphatase receptor-like genes are frequently hypermethylated in sporadic colorectal cancer. J Hum Genet 58, 11–15 (2013). https://doi.org/10.1038/jhg.2012.119
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DOI: https://doi.org/10.1038/jhg.2012.119
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